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To review changes in the medical complications of drug abuse that have occurred since the authors reviewed them 25 years ago.Manual search of the internal medicine and subspecialty literature of the past three decades that was selected by the authors.Selected studies were of three types—baseline studies for the period ending in 1968, studies after 1968 that emphasized changes from baseline, and studies after 1968 that emphasized change (or the absence of change) and the manner in which clinicians conceptualized problems.We extracted data that showed changes in the diseases, the appearance of new diseases, or the disappearance of formerly common diseases.The diseases complicating drug abuse are now more widely disseminated than they were in the last 25 years. Some former “diseases of addiction” such as tetanus and malaria are now rare. Diseases (such as human immunodeficiency virus infection) not known to exist or rare 25 years ago now occur frequently. The drugs of abuse have also changed; for example, cocaine is now much more common.Treating the acute medical problems (mostly infectious diseases) in poor, undereducated, and often noncompliant intravenous drug users is far more complex than previously described. Although some features have remained constant, the emergence of human immunodeficiency virus infection and changes in patterns of drug use have radically altered patient management.