Aplastic anemia is a form of bone marrow failure that ranges in severity from mild to severe. In all cases, some degree of pancytopenia is present. The cause usually is unknown, although many drugs and viruses are associated with the disease. The pathophysiology of aplastic anemia involves either a stem cell defect or injury or an immunologically mediated hematopoietic cell destruction, which may operate in concert with abnormalities in programmed cell death. Excellent clinical care and research have dramatically improved patient survival, with 70% to 90% of sibling hematopoietic stem cell transplant recipients surviving long term. Patients with mild or moderate disease may not require immediate treatment. If and when these patients require treatment, the mainstay of therapy is immunosuppression. The initial drug regimen includes antithymocyte globulin, often in combination with cyclosporine A, followed by moderate-dose steroids and cyclophosphamide. Nurses assess and monitor patients and their progress, recognizing medication adverse effects. Nurses educate patients about their disease and its treatment, and provide necessary emotional support. Severe aplastic anemia is treated with allogeneic hematopoietic stem cell transplantation. This therapy involves complex nursing challenges. The patient goes through an extensive pretransplantation workup. Donor selection and harvesting of hematopoietic stem cells are preludes to an intensive preparative regimen. This preparative or conditioning regimen and the need for long-term immunosuppression are the reasons for many of the acute complications and adverse events that may follow the hematopoietic stem cell transplantation. Nurses must be vigilant in assessing and monitoring patients for toxicities and long-term complications that may affect almost any organ system.