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In October 1999, nineteen private organizations filed a rulemaking petition with the EPA requesting regulation of greenhouse gas emissions from new motor vehicles under section 202 of the Clean Air Act. The petition asserted that carbon dioxide and other gases were heat-trapping greenhouse gases that had accelerated climate change, with carbon dioxide as the most important contributor according to the IPCC's 1995 report. The EPA received more than fifty thousand comments after requesting public input in 2001. A National Research Council report from 2001, prepared at the White House's request, stated that greenhouse gases from human activities were causing surface air temperatures to rise. On September 8, 2003, the EPA denied the petition on two grounds: the Clean Air Act did not authorize regulation of greenhouse gases from motor vehicles, and even assuming authority, the agency would not regulate due to scientific uncertainty about causation and concerns that regulation would conflict with the President's comprehensive approach involving voluntary programs and international negotiations. The denial order referenced Congress's decision in 1990 not to enact binding emissions limitations and the political history of climate change issues. Petitioners including the Commonwealth of Massachusetts and other states and private organizations then sought review in the United States Court of Appeals for the District of Columbia Circuit. The D.C. Circuit denied the petition for review in 2005. The Supreme Court granted certiorari in 2006 to address the issues raised by the denial. Massachusetts submitted affidavits showing that global sea levels rose 10 to 20 centimeters over the 20th century, already causing loss of coastal land owned by the Commonwealth, with projections of further inundation by 2100. The United States transportation sector alone emitted more than 1.7 billion metric tons of carbon dioxide in 1999, accounting for over 6 percent of worldwide emissions.

Two minors brought suit against Merrell Dow Pharmaceuticals, claiming they suffered limb reduction birth defects because their mothers had taken Bendectin, a drug prescribed for morning sickness to about 17.5 million pregnant women in the United States between 1957 and 1982. Limb reduction defects occur in fewer than one birth out of every 1000. Scientists do not know the mechanism by which any teratogen causes such defects. The plaintiffs offered testimony from three groups of experts. One group proposed to testify to a statistical link between Bendectin ingestion during pregnancy and limb reduction defects based on reanalyses of published studies that had reported no such association. A second group proposed to testify that Bendectin causes limb reduction defects in humans because it causes such defects in laboratory animals. A third group proposed to testify based on the similarity of Bendectin's chemical structure to other drugs suspected of causing birth defects. The district court granted summary judgment to Merrell Dow after excluding the plaintiffs' expert testimony. The Ninth Circuit affirmed that decision. The Supreme Court granted certiorari, reversed, and remanded for consideration under Federal Rule of Evidence 702. On remand, the Ninth Circuit examined the affidavits and prior trial testimony of the plaintiffs' experts. None of the experts had studied the effect of Bendectin on limb reduction defects before being hired to testify in this or related cases. None had published his work on Bendectin in a scientific journal. The only review their work had received was by judges and juries. Plaintiffs' epidemiological experts made vague assertions of a statistically significant relationship between Bendectin and birth defects but did not state that the relative risk exceeded two. With the exception of Dr. Palmer, the remaining experts were willing to testify only that Bendectin is capable of causing birth defects. Dr. Palmer alone was willing to testify that Bendectin did cause the limb defects in each of the children, based on his review of the plaintiffs' medical records and his conclusion that Bendectin is a teratogen.

In 2001, three current or former female employees of Wal-Mart Stores, Inc.—Betty Dukes, Christine Kwapnoski, and Edith Arana—filed a lawsuit in the Northern District of California alleging that the company had discriminated against them and other women in pay and promotions. Wal-Mart, the nation’s largest private employer with approximately 3,400 stores across the country and more than one million employees, delegated pay and promotion decisions to local store managers who exercised broad discretion in a largely subjective manner. The plaintiffs claimed that this discretion was exercised disproportionately in favor of men, resulting in lower pay and fewer promotions for female employees. They sought to represent a class of approximately 1.5 million current and former female employees who had worked at any Wal-Mart domestic retail store since December 26, 1998. To support their motion for class certification, the plaintiffs presented statistical evidence from experts Dr. Richard Drogin and Dr. Marc Bendick showing pay and promotion disparities between men and women, anecdotal evidence consisting of about 120 affidavits from female employees describing discriminatory experiences at only 235 of the company's 3,400 stores, and the testimony of sociologist Dr. William Bielby who analyzed Wal-Mart’s corporate culture. Betty Dukes began working at a Pittsburg, California store in 1994 as a cashier and was later promoted to customer service manager before being demoted; she alleged retaliation and that male greeters were paid more. Christine Kwapnoski worked at Sam’s Club stores and claimed a male manager yelled at female employees and told her to “doll up.” Edith Arana worked at a Duarte, California store from 1995 to 2001. She was denied opportunities for management training despite repeated requests. The District Court certified the class under Federal Rule of Civil Procedure 23(b)(2), finding that the plaintiffs had presented significant evidence of a company-wide pattern of discrimination. The Court of Appeals for the Ninth Circuit, sitting en banc, substantially affirmed the certification order. The Supreme Court granted certiorari to review whether the class certification was consistent with Rule 23(a) and (b)(2).

Hustler Magazine, Inc., a magazine of nationwide circulation, and its publisher Larry Flynt published a parody of a Campari Liqueur advertisement in the November 1983 issue. The parody featured respondent Jerry Falwell and suggested that his first time sampling the liqueur occurred during a drunken incestuous rendezvous with his mother in an outhouse. The parody included a disclaimer in small print that it was an ad parody not to be taken seriously. Falwell filed suit in the United States District Court for the Western District of Virginia seeking damages for libel, invasion of privacy, and intentional infliction of emotional distress. The District Court directed a verdict against Falwell on the privacy claim. The jury found against respondent on the libel claim but awarded Falwell $100,000 in compensatory damages and $50,000 in punitive damages from each petitioner on the emotional distress claim. The United States Court of Appeals for the Fourth Circuit affirmed the judgment. The Supreme Court granted certiorari given the importance of the constitutional issues involved.