Several recreational, prescription, and illicit drugs have psychotropic effects that may be perceived to be ergogenic. The ephedra alkaloids have received recent attention for their wide use by athletes and their potential serious side effects, despite the lack of evidence regarding any ergogenic or performance benefit. Some prescription drugs (eg, methylphenidate and bupropion) raise complex issues regarding their appropriate therapeutic use in athletes. Recreational drugs, some of which are illegal (eg, cocaine), are commonly used by athletes and cause a wide range of potentially ergolytic effects. In total, these drugs are important for their frequent use, the frequency with which they are mentioned in the media, and their potential for causing significant adverse effects.