The clinical outcome of acute myeloid leukemia (AML) is extremely variable, ranging from survival of a few days to cure. Different clinical and biological features at diagnosis have been reported as useful for the prediction of clinical outcome; however, in most AML cases induction therapy must be initiated as soon as possible, therefore, the possibility of stratifying patients at diagnosis is generally not taken into account, with the exception of acute promyelocytic leukemia in which morphology, immunophenotype, and molecular biology allow a rapid diagnosis and the adoption of specific therapy. As a consequence, prognostic factors in AML are more useful for the prediction of relapse, rather than for the stratification of induction therapy. Most relevant studies, based on large multicenter trials have definitively demonstrated that age and cytogenetics at diagnosis are the most important prognostic determinants for patients with AML. Early blast clearance after induction chemotherapy represents a further important factor of potential utility into clinical practice. Finally, biologic parameters, such as mutations of FLT3 and nucleophosmin, have been reported as useful for the prognostic categorization mainly in patients with intermediate cytogenetics and can also represent potential targets for new therapeutic agents.