Psychoactive substances have been used by humans from the earliest recorded times, and evidence shows that from the beginning some people have used drugs excessively, thus developing problems. From the 1960s to the 1980s, there has been a dramatic upswing in the use of alcohol and illicit substances, but some evidence demonstrates that this trend is beginning to reverse. Current substance abuse is estimated to cost US society about $152 billion and cause over 75,000 deaths annually. Research and treatment efforts have increased significantly over the past two decades. Although the exact cause of substance abuse disorders is unknown, evidence indicates that it is a complex interaction between biologic predispositions, and psychologic and social factors. The majority of research seems to indicate that at least in a subtype of patients with more severe abuse, genetic factors appear to be the single most important influence. Considerable research is underway to further clarify these factors, and it is reasonable to expect that we will soon have a much clearer understanding of the cause of these disorders. In turn, this understanding should lead to a better understanding of the optimal treatment for the millions of patients and families afflicted with substance abuse disorders.