Lower-extremity (LE) musculoskeletal disorders (MSDs) can have a major impact on the ability to carry out daily activities. The effectiveness of interventions must be examined to enable occupational therapy practitioners to deliver the most appropriate services. This systematic review examined the literature published between 1995 and July 2014 that investigated the effectiveness of occupational therapy interventions for LE MSDs. Forty-three articles met the criteria and were reviewed. Occupational therapy interventions varied on the basis of population subgroup: hip fracture, LE joint replacement, LE amputation or limb loss, and nonsurgical osteoarthritis and pain. The results indicate an overall strong role for occupational therapy in treating clients with LE MSDs. Activity pacing is an effective intervention for nonsurgical LE MSDs, and multidisciplinary rehabilitation is effective for LE joint replacement and amputation. Further research on specific occupational therapy interventions in this important area is needed.