Correct diagnosis of cold agglutinin disease represents the key to the successful treatment. Warm antibodies are absent and hemolysis is caused by antibodies of the IgM class that are typically present in the form of paraprotein – the disorder shows features of low-grade lymphoproliferation. Steroids are not active the basic component of the treatment is rituximab that is combined in order to improve the efficacy of the therapy with other cytostatic drugs, more recently with bendamustine or bortezomib. Eculizumab can be successfully used in the cases of significant resistance to the combined immuno-chemotherapy.