The carpometacarpal (CMC) of the thumb is a saddle joint that permits a wide range of motion and is largely responsible for the characteristic dexterity of human prehension. This joint, located at the very base of the thumb, is subject to large physical stresses throughout life. Osteoarthritis (posttraumatic or idiopathic), rheumatoid arthritis, and postmenopausal laxity of the capsular ligaments can predispose structural instability and impairment of this important joint. The instability is characterized by varying and often progressive dislocation of the joint surfaces, resulting in a displaced axis of rotation and abnormal actions of thumb muscles. The main consequence of the instability is most often pain and weakness, most notably during pinch and grasping actions. This paper is conceptually divided into 2 sections. The first section describes the anatomic structures that maintain stability in the normal CMC joint of the thumb and how disease or trauma can cause instability and ultimate deformity. The second section describes both nonsurgical and surgical interventions that are most often used to treat an unstable CMC joint. This paper is intended primarily as an overview for the physical therapist who does not specialize in the treatment of the hand, although desires basic information on this important topic.