Major advances in the treatment of B-cell lymphoma resulting from the introduction of a monoclonal antibody to the CD20 antigen 15 years ago have left Hodgkin lymphoma (HL) aside. This has changed with the success of the anti-CD30 antibody conjugated with an antitubulin agent, brentuximab vedotin, recently approved for the treatment of adult patients with relapsed or refractory CD30+ HL following autologous stem cell transplantation (ASCT) or following at least two prior therapies when ASCT or for which multi-agent chemotherapy is not a treatment option. The magnitude of clinical activity of the new antibody has also prompted research on biologic functions of the CD30 molecule, as well as exploring other potential targets present on multinucleated Reed–Sternberg cells and the surrounding inflammatory area for a range of antibodies. This article will review the accumulating clinical data on the use of monoclonal antibodies in the treatment of classical HL with focus on CD20 and CD30 targets. We describe possible mechanisms of action, efficacy and toxicity related to administration of rituximab, brentuximab vedotin, daclizumab and other antibodies investigated in Phase I and II trials for classical HL.