Osteopetrosis, an inherited disorder of bone metabolism, is associated with multiple musculoskeletal complications. Two of these problems, osteoarthritis and periarticular nonunions, may be considered for treatment with total joint arthroplasty. However, there is little information on the early and longer-term results, complications, and technical difficulties related to performing arthroplasty in patients with osteopetrosis. We report the results of 3 total hip arthroplasties and 2 total knee arthroplasties in patients with osteopetrosis. These cases in combination with a literature review provide further insight into results, complications, and technical challenges of performing total joint arthroplasty in patients with osteopetrosis.