Cold agglutinin disease (CAD) is a rare, autoimmune hemolytic anemia in which cold-reacting autoantibodies (cold agglutinins) bind to normal antigens on the surface of red blood cells during passage through the cooler peripheral circulation. These antibodies cause agglutination of red blood cells, leading to an immune response and premature destruction of the healthy red blood cells. The authors have written this resource to give clinicians the information they need to successfully diagnose and manage CAD in adult patients.