Aggressive T-cell lymphomas are a heterogeneous group of malignancies of mature T and natural killer cells, many of which have recently been identified as distinct entities in the classification of non-Hodgkin lymphomas according to the World Health Organization. Owing in part to a limited understanding of the molecular features and pathogenesis of many of these disorders, treatment strategies using conventional lymphoma regimens have been used, with generally inferior outcomes. Recent data are now emerging from gene expression profiling and molecular analysis of tumors, which has led to development of novel, targeted therapeutic strategies and has provided a basis for more accurate diagnosis and prognostic characterization.