A systematic review of the literature related to effective occupational therapy interventions in rehabilitation of individuals with work-related forearm, wrist, and hand injuries and illnesses was conducted as part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association. This review provides a comprehensive overview and analysis of 36 studies that addressed many of the interventions commonly used in hand rehabilitation. Findings reveal that the use of occupation-based activities has reasonable yet limited evidence to support its effectiveness. This review supports the premise that many client factors can be positively affected through the use of several commonly used occupational therapy-related modalities and methods. The implications for occupational therapy practice, research, and education and limitations of reviewed studies are also discussed.