T-cell and natural killer-cell lymphomas are a relatively rare and heterogeneous group of diseases that are difficult to treat and usually have poor outcomes. To date, therapeutic interventions are of limited efficacy and there is a pressing need to find better treatments. In recent years, advances in molecular biology have helped to elucidate the underlying genetic complexity of this group of diseases and to identify mutations and signaling pathways involved in lymphomagenesis. In this review, we highlight the unique biological characteristics of some of the different subtypes and discuss how these may be targeted to provide more individualized and effective treatment approaches.