Children of substance abusing parents have an elevated risk for experiencing disruptions in household composition and for engaging in problem behaviors. This study investigated whether multiple parent figure transitions predicted the likelihood of delinquency and drug use among a sample of early adolescents with parents receiving methadone treatment for opiate addiction. Controlling for baseline delinquency, child characteristics, family conflict, parental depression, and parent criminal history, a greater number of parenting disruptions during the longitudinal study period was associated with a higher probability of delinquent behavior. Gender moderated the effect of parent figure transitions in a parallel analysis for drug use. After accounting for baseline drug use and potentially confounding factors, only adolescent females had a higher likelihood of drug use as the number of family disruptions increased. In contrast, age was strongly associated with drug use for males. A subgroup of youths who experienced tremendous family instability and had no single consistent parent figure during the study period were at extreme risk for delinquent behavior. The findings are interpreted in terms of cumulative stress resulting from multiple parenting disruptions over time and differential influences on the expression of problem behaviors depending on gender.