Treatment of refractory or relapsed classical Hodgkin lymphoma (HL) remains challenging, but targeted immunotherapy has recently emerged as a potential treatment option for these patients. Although first-generation monoclonal anti-CD30 antibodies proved disappointing, current efforts to modify anti-CD30 antibodies to improve binding of effector cells and enhance activity appears more promising, as does the development of novel antibody-drug conjugates (ADCs). ADCs offer the potential to deliver potent therapies with minimal toxicity. One highly active ADC, brentuximab vedotin (SGN-35), combines an anti-CD30 monoclonal antibody and the antitubulin agent monomethyl auristatin E. Initial phase 1 studies of brentuximab vedotin showed a 52% overall response rate in relapsed HL, with minimal toxicity. This article highlights the development of anti-CD30 antibodies and ADCs for relapsed or refractory classical HL.