Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin lymphomas that are less chemosensitive than their B-cell counterparts. Until recently, standard therapy did not distinguish between subtypes, and deeper understanding of the biology of these diseases was lacking. The availability of targeted therapy and more sophisticated subtype classification has translated into the development of novel treatment options for these rare diseases. This includes the development of a brentuximab vedotin-based upfront chemotherapy regimen that confers an overall survival benefit for a subset of patients. Clinical trials of targeted agents, as well as development of better preclinical models of PTCL, are leading to therapeutic advances in the field, including the development of phosphoinositide-3-kinase inhibitors, histone deacetylase inhibitor-based strategies, CD30-directed strategies, Janus kinase inhibitors, and spleen-associated tyrosine kinase inhibitors. Better understanding of the biology of these diseases based on gene expression profiling, minimal residual disease evaluation, and modeling in patient-derived xenografts should help define mechanisms of response and resistance to therapy. Given the complex biology of these heterogeneous lymphomas, well-tolerated combination strategies targeted toward specific subtypes of PTCL can lead to advances in the field. Similar to the story of brentuximab vedotin, development of effective therapies in the salvage setting will likely lead to improved upfront strategies in PTCLs, and ultimately a more personalized approach.