Single-agent topotecan is an active drug in chemotherapy-naive MDS and CMML and, to a lesser degree, in refractory/relapsed acute leukemias, low-/intermediate-grade lymphoma, and myeloma. Its combination with cytosine arabinoside induces complete remissions in high-risk MDS/CMML. A triplecombination regimen of cyclophosphamide, cytosine arabinoside, and topotecan (CAT) was extensively tested in refractory/relapsed as well as in untreated AML. By proving effective in inducing complete remission in newly diagnosed AML at rates comparable to those achieved by anthracycline-cytosine arabinoside regimens, for example, CAT offers a useful treatment alternative. Topotecan combined with paclitaxel is promising in low-/intermediate-grade lymphomas. The activity of topotecan justifies further evaluation of topotecan-containing combination regimens, particularly in MDS/CMML and acute leukemias.