Peripheral blood cytopenias and dysplastic hematopoietic progenitors characterize the myelodysplastic syndrome. Patients suffer from the consequences of chronic cytopenias or progression to acute myelogenous leukemia. Although allogeneic hematopoietic stem cell transplantation is a potentially curative option, the standard of care for most patients with myelodysplastic syndrome continues to be supportive care, with blood product transfusion and antibiotics for infectious complications. Many patients with myelodysplastic syndrome are not candidates for allogeneic hematopoietic stem cell transplantation because of advanced age, comorbid illnesses, and lack of a histocompatible donor. Increased rates of apoptosis in hematopoietic progenitors, altered production of inflammatory cytokines, neoangiogenesis, and autoreactive T lymphocytes have all been shown to contribute to the phenotype of myelodysplastic syndrome. These recent insights into the pathophysiology of myelodysplastic syndrome have been translated into therapeutic trials of noncytotoxic agents for this disorder. Although clinical responses have been seen with these novel agents, the critical biologic targets have not yet been clearly defined. © 2003 Lippincott Williams & Wilkins, Inc.