Historically, substance use problems were thought to be more prevalent in lesbian, gay, and bisexual (LGB) populations, and correcting skewed perceptions about substance abuse among LGB individuals is critically important. This review provides an update on empirical evidence on LGB substance use patterns and treatment outcome, with specific focus on clinical implications of findings. Compared to earlier studies, the recent research included in this review has used more sophisticated methodologies and more representative samples, and also has investigated multiple dimensions of sexual orientation in relation to substance use patterns. Findings from recent research suggest that lesbians and bisexual women are at greater risk for alcohol and drug use disorders and related problems, and that gay and bisexual men are at greater risk for illicit drug use and related problems. Several sociocultural factors have emerged as correlates of substance use patterns in LGB populations (e.g., affiliation with gay culture, HIV status), and several demographic characteristics (e.g., female, older age) do not appear to be as robust of protective factors against substance abuse for LGB individuals compared to heterosexual populations. Bisexual identity and/or behavior in particular seem to be related to increased risk for substance abuse. In terms of treatment outcome, limitations of extant research prevent conclusions about the relative impact of LGB-specific interventions, and further research that includes women and uses more equivalent comparison interventions is needed. Clinical implications of research findings are discussed for case identification, selection of treatment goals (e.g., moderation vs. abstinence), targets for intervention, and specific treatment modalities.