OBJECTIVE. The purpose of this systematic review was to describe the evidence for the effectiveness of early intervention to improve and maintain performance in occupations for youths with or at risk for serious mental illness (SMI). METHOD. Titles and abstracts of 670 articles were reviewed, 234 were retrieved for full review, and 30 met inclusion criteria. RESULTS. Moderate to strong evidence supports cognitive remediation (CR) and mixed evidence supports cognitive-behavioral therapy (CBT) as an adjunct modality to improve general functioning. Moderate to strong evidence supports use of supported employment and supported education (SE/E) to improve social and occupational outcomes in employment and academics. Strong evidence supports family psychoeducation (FPE) to prevent relapse and rehospitalization and improve problem-solving skills and general functioning. CONCLUSION. Occupational therapy practitioners should integrate CR, SE/E, and FPE into early intervention with youth with or at risk for SMI. In addition, CBT is an effective modality for use with this population.