The mortality for dogs with severe immune-mediated hemolytic anemia (IMHA) is unacceptably high, and better immunosuppressive regimens are needed to increase survival. Understanding the basic immunology of the disease and the mechanisms of action of the available immunosuppressive therapies will help clinicians choose an appropriate immunosuppressive protocol. Prospective, randomized clinical studies must be conducted to evaluate the efficacy and safety of different combined immunosuppressive modalities to treat canine IMHA and improve patients' outcomes.