Arthritis of the glenohumeral joint is a common cause of debilitating shoulder pain, affecting up to one-third of patients older than 60 years. It is progressive in nature and characterized by irreversible destruction of the humeral head and glenoid articular surfaces. Inflammation of the surrounding soft tissues is often present and further contributes to the pain caused by the disease process. A number of primary (degenerative) and secondary pathological processes may result in this condition. Patients often present with a long history of shoulder pain, stiffness, and/or loss of function, or may have acute exacerbations of this chronic condition. Initial conservative management is aimed at improving pain and restoring function. Surgical treatment is indicated in severe or refractory cases when nonoperative management has failed. Shoulder replacement now accounts for the third most common joint replacement surgery after the hip and knee. This article reviews the basic science and clinical management of osteoarthritis of the glenohumeral joint.