Hematologic adverse events (AEs) are commonly encountered in patients with multiple myeloma (MM) owing to the nature of the disease and the adverse effects related to myeloma treatment. Immunomodulatory drugs (eg, thalidomide, lenalidomide, and pomalidomide) and the proteasome inhibitor bortezomib have all been associated with increased rates of anemia, neutropenia, and thrombocytopenia, as well as greater incidences of infection caused by associated immunosuppression. The proteasome inhibitor carfilzomib was recently approved in the United States for the treatment of patients with relapsed and refractory MM. This article reviews the hematologic safety profile of carfilzomib in patients with relapsed/refractory MM, as assessed in a cross-trial safety analysis of four phase II studies, and makes recommendations for the appropriate management of hematologic AEs.