The identification of biologic markers for disease outcome in hematopoietic malignancies is essential for the development of "risk-adapted" therapies. Although new prognostic factors are frequently described, their real clinical and biologic impact is often difficult to determine. Factors that influence a marker's true prognostic value include several variables of study design: study size, uniform versus nonuniform patient treatment, methodologic variations, and correlations with other variables. Despite these concerns, several important prognostic factors have emerged in acute leukemias. For example, in acute myeloid leukemia, the multidrug resistant phenotype, whether conferred by the classic P-glycoprotein (multidrug resistance protein 1) or by other mechanisms, and cytogenetics are major prognostic indicators for outcome. In acute lymphoblastic leukemia, markers associated with loss of growth control (loss of tumor suppressor genes, increased proliferative fraction) likewise identify a group of poor-prognosis patients. The delineation of prognostic factors such as these allows for the better identification of patients who may benefit from risk-adapted therapies.