This paper selectively reviews current knowledge about the effects of alcohol, cocaine, and marijuana. Highlights of the review include findings that: (1) gender differences in alcohol and polysubstance users are reflected in epidemiological, biobehavioral, and neuroendocrine factors; (2) women and men exhibit different patterns of alcohol consumption, and also differently absorb and metabolize alcohol; (3) onset of dependence in women appears truncated, and women and men experience different social consequences; (4) gender differences also occur in cocaine and in marijuana users; (5) women who use cocaine are more likely to experience depressive symptoms, and women who smoke marijuana are less likely to accelerate smoking rates; and (6) accumulating evidence points to some contribution of family history of alcoholism to polysubstance use, and all substances have deleterious effects on the reproductive system. Six areas for future research are suggested. These focus on researching effects of substances on the neuroendocrine system; individuals presenting for treatment with dual diagnoses; the need to analyze broad factors influencing substance use; changing patterns of substance abuse; and primary prevention. Seven tables and a bibliography of 63 references are included. (Author/ABL)