Cold Agglutinin Disease is a rare, chronic hemolytic disorder, representing approximately 20% of all autoimmune hemolytic anemias. Catherine M. Broome, MD, and Alexander Röth, MD, provide an understanding of the pathogenesis of this disorder caused by cold-reacting IgM autoantibodies and reveal common clinical features. Because of the high mortality rate among those suffering from CAD, it is important to be aware of the diagnostic criteria, as well as the current and novel treatment options, with the goal of increasing hemoglobin levels, avoiding the need for transfusions, and improving circul