Alloantibodies clearly cause acute antibody mediated rejection, and all available evidence supports their pathogenic etiology in the development of chronic alloantibody mediated rejection (CAMR). But the slow evolution of this disease, the on-going immunosuppression, the variations in titer of alloantibodies, and variation in antigenic targets all complicate identifying which dynamic factors are most important clinically and pathologically. This review highlights the pathological factors related to the diagnosis of CAMR, the time course and natural history of this disease. What is known about CAMR pathogenesis is discussed including alloantibodies, the role of complement, gene activation, and Fc effector cell function. Therapy, which is problematic for this disease, is also discussed, including on-going and potential therapies and their limitations.