Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL) are the most frequent of more than 20 mature PTCL entities featuring a broad spectrum of morphological, immunophenotypic, molecular and clinical characteristics. Unfortunately, recent progress in understanding the (epi)genetic background of PTCL has not been met with similar advances in treatment. Thus, CHO(E)P [cyclophosphamide, doxorubicin, vincristine, and prednisone (plus etoposide)] remains standard first-line therapy. Patients without comorbidities achieving complete or partial remission proceed to autologous stem cell transplantation. With this approach about 50% of patients survive long-term. Patients relapsing after or progressing during first-line therapy have a dismal prognosis. They receive salvage gemcitabine-therapy followed by allogeneic transplantation whenever possible. After allografting, approximately half of the patients survive long-term; any other treatment is palliative. New drugs investigated in phase II studies achieved response rates between 10% and 30%; long-term remissions are the exception to the rule. While most new drugs are not licensed and not readily available, a plethora of other innovative drugs targeting (epi-)genetic abnormalities are in early development. These, together with combinations of new and old drugs, will hopefully increase response to first-line therapy, bridge more patients to transplantation, and finally improve prognosis for all patients with PTCL.