This study examined the relationships between self-reported childhood sexual abuse (CSA) and drug-related outcomes in an Australian twin panel. A semi-structured psychiatric interview was conducted in 1996-2000 by telephone with young adult Australian twins (mean age 29.9 years). Data reported here are from 6050 twins who responded to both CSA and drug-related items. A history of CSA was associated with significant risk for subsequently occurring regular smoking and use of each illicit drug class. Further CSA-associated risk was found among regular users, for nicotine and alcohol dependence, and among illicit drug users, for abuse/dependence of most drug classes. In same-sex discordant pairs, significant risk for regular smoking and illicit drug use was found in twins with a history of CSA compared to their non-abused co-twins. Similar analyses for abuse/dependence found significant risk for opioids, any illicit drug, and any non-cannabis illicit drug. CSA was associated with significantly earlier drug use. Despite the association of CSA with risk for early-onset cannabis use and regular smoking, risks for illicit drug outcomes associated with CSA and with either form of early-onset use combine in near-additive fashion. CSA is associated with risk for subsequently occurring regular smoking and illicit drug use and abuse/dependence. Risks for drug use are mildly attenuated with control for familial contributions; similar risks for abuse/dependence remain significant for opioids and for illicit drugs combined across classes. Although we found evidence of earlier onset drug use with CSA, risks associated with CSA and with early-onset use combine in a largely additive manner.