The mechanisms through which multisystemic therapy (MST) decreased delinquent behavior were assessed in 2 samples of juvenile offenders. Sample 1 included serious offenders who were predominantly rural, male, and African American. Sample 2 included substance-abusing offenders who were predominantly urban, male, and Caucasian. Therapist adherence to the MST protocol (based on multiple respondents) was associated with improved family relations (family cohesion, family functioning, and parent monitoring) and decreased delinquent peer affiliation, which, in turn, were associated with decreased delinquent behavior. Furthermore, changes in family relations and delinquent peer affiliation mediated the relationship between caregiver-rated adherence and reductions in delinquent behavior. The findings highlight the importance of identifying central change mechanisms in determining how complex treatments such as MST contribute to ultimate outcomes.