Cold agglutinin disease is a normo- or macrocytic anemia due to antibodies, active under body temperature, mostly belonging to the immunoglobulin class M. Initially the agglutination of erythrocytes with acrocyanosis is reversible at body temperature. High antibody activity or long lasting period of coldness lead to intravascular or intrahepatic hemolysis, but high risk anemia is rare. Beside the idiopathic form, infection induced (especially infectious mononucleosis, cytomegalovirus, Mycoplasma pneumoniae, Klebsiella), and drug induced (especially quinidine, alpha methyldopa, penicillin, para-aminosalicylic acid, various analgetics, sulfonylurea), tumor associated (especially malignant lymphomas), and autoimmune disease associated (especially systemic lupus erythematosus) cold agglutinin anemias are discribed. "Cross reacting antigenity" to the hemolysing agent and the membrane of erythrocyte, exogenous induced changing of erythrocytic antigenity, and diversification concerning the production of antibodies are discussed as pathophysiological explanations.