Therapeutic apheresis (TA), as a way of rapidly eliminating harmful or excessive blood components such as plasma proteins (plasma exchange) or cells (leukapheresis and platelet apheresis), has found broad application in a vast array of hematologic disorders. The most common hematologic indications for TA are leukocytosis in acute leukemias and hyperviscosity syndrome secondary to plasma cell dyscrasia. Leukapheresis is indicated in the initial management of leukostasis in patients with hyperleukocytosis in acute leukemias, particularly myeloid leukemias, or in patients who are at high risk of developing such a complication. Patients with lymphoid malignancies rarely develop leukostasis but may undergo cytoreduction with leukapheresis as prophylaxis for tumor lysis. The use of leukapheresis in acute promyelocytic leukemia is discouraged, given the possibility of increased risk of coagulopathy and bleeding. Similarly, therapeutic plasma exchange (TPE) represents an effective but temporary way of managing hyperviscosity syndrome secondary to immunoglobulin M paraproteins in patients with Waldenström macroglobulinemia. This review provides an overview of the pathophysiology of leukostasis and its management with leukapheresis. The use of TPE in the management of hyperviscosity syndrome is also discussed.