Mature T-cell and natural killer (NK)-cell lymphomas are rare neoplasms, differing geographically in frequencies. T-cell lymphomas are more common in Asia than in western countries, and NK-cell lymphomas occur almost exclusively in Asia and South America. The rarity of these lymphomas means that treatment algorithms of T-cell and NK-cell lymphomas have not been well established. Angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, are the more commonly encountered T-cell lymphomas. Treatment with anthracycline-based regimens designed for aggressive B-cell lymphomas gives unsatisfactory results. Cutaneous T-cell lymphomas may remain indolent, but outcome is poor for advanced diseases. Novel therapies, including monoclonal antibodies, nucleoside analogs, histone deacetylase inhibitors and small molecules targeting cellular signaling pathways, are being explored alone or in combination with chemotherapy. High-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is recommended for high-risk cases. NK-cell lymphomas exhibit the multidrug resistance phenotype due to P-glycoprotein expression, so that anthracycline-based regimens are ineffective. Non-multidrug resistance-dependent regimens and L-asparaginase-based protocols have been shown to be highly active. Autologous HSCT is not routinely performed. The role of allogeneic HSCT is being examined.