The multidrug transporter, P-glycoprotein (P-gp), is expressed by CD34-positive bone marrow cells, which include hematopoietic stem cells, and in other cells in the bone marrow and peripheral blood, including some lymphoid cells. Multidrug resistance mediated by P-gp appears to be a major impediment to successful treatment of acute myeloid leukemias and multiple myelomas. However, the impact of P-gp expression on prognosis has to be confirmed in several other hematopoietic neoplasms. The role of P-gp in normal and malignant hematopoiesis and clinical attempts to circumvent multidrug resistance in hematopoietic malignancies are reviewed. The recent transduction of the MDR1 gene into murine hematopoietic cells, which protects them from toxic effects of chemotherapy, suggests that MDR1 gene therapy may help prevent myelosuppression following chemotherapy.