This article reviews the current knowledge of therapeutic targeting of CD30+ cancers using naked and conjugated monoclonal antibodies.After unsuccessful outcome of early trials using naked and conjugated anti-CD30 antibodies, substantial progress was achieved with the development of the antibody-drug-conjugate brentuximab vedotin. In two recently completed phase II studies in patients with relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL), the single agent response rates were 75 and 86%, respectively. These impressive results led to the recommendation of the Oncology Drug Advisory Committee for an accelerated approval of brentuximab vedotin by the Food and Drug Administration.Brentuximab vedotin demonstrated the most potent single agent activity for the treatment of patients with relapsed Hodgkin lymphoma and ALCL. Incorporating brentuximab vedotin with frontline regimens is currently being evaluated in clinical trials.