Psychoactive medications are often reported as delirium risk factors in hospitalized patients, and delirium induced by medication is potentially avoidable. The authors critically reviewed the evidence for a role of medications in delirium etiology. Only a few positive associations were noted. Use of psychoactive medications, considered together as a single variable, and use of opioids increased the risk of delirium. Data were scarce and sometimes conflicting, and methodological limitations were often present. The suspected association between psychoactive drugs and delirium cannot be unambiguously confirmed with current epidemiological evidence. The interpretation of these results must take into account the limitations of published studies, which should be addressed in future research.