Peripheral T-cell lymphomas (PTCLs) are a heterogeneous collection of lymphomas that are associated with very poor prognosis. Conventional therapies, historically based on protocols for aggressive B-cell lymphomas, deliver less than adequate outcomes; the majority of patients experience early relapse after front-line treatment and current 5-year overall survival is only 10-30%. Clearly, new approaches are needed. In recent years there has been a plethora of novel agents showing activity in PTCL, often in patients with advanced relapsed or refractory disease. These agents include antifolate drugs (pralatrexate), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat and belinostat), nucleoside analogues (gemcitabine, forodesine and clofarabine), monoclonal antibodies (anti-CD52, anti-CD4 and anti-CD2), fusion toxins (denileukin diftitox), immunomodulatory agents (lenalidomide) and proteasome inhibitors (bortezomib). This is an exciting time in the treatment of PTCL, as our ever improving understanding of the distinguishing features, pathogenesis, molecular biology and progression of PTCL, and the knowledge of the mechanism and efficacy of novel therapies, may see a real improvement in outcomes for patients. The purpose of this article is to focus on these novel therapies and the results of recent clinical trials in PTCL.