The goal of front-line therapy in any aggressive lymphoma is to achieve a long-term remission and cure from the disease. For peripheral T-cell lymphomas (PTCLs), though, the success of front-line therapies is still limited, and is challenged by high rates of primary refractory disease and early relapses, often with fatal outcomes. For risk stratification, the International Prognostic Index is commonly used for all subtypes of nodal PTCLs and recommended by international treatment guidelines. For the most common subtypes of PTCL, including PTCL-not otherwise specified and angioimmunoblastic T-cell lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy remains the widely accepted standard for induction therapy. In patients with anaplastic lymphoma kinase anaplastic large-cell lymphomas, high baseline TMVT and poor interim positron emission tomography response predicted disease progression or death within the first year, suggesting early allogeneic transplantation or innovative therapies for this population.