Many new approaches involving the use of antibody-based agents have produced promising results in experimental Hodgkin's lymphoma (HL) models. Early clinical trials using immunotoxins, radioimmunotherapy (RIT), bispecific molecules and monoclonal antibodies (mAbs), have demonstrated some clinical efficacy in patients with advanced refractory HL. Although it seems unlikely that these approaches alone will cure chemotherapy-resistant patients with larger tumor masses, combination with conventional chemotherapy may help to overcome resistance of Hodgkin-Reed/Sternberg (H-RS) cells or to eliminate residual disease. Since H-RS cells are extremely sensitive to irradiation, RIT may be a potential approach. A murine mAb (Ki-4)-based 131I conjugate showed efficacy in refractory HL patients, however, toxicity was a problem and less toxic constructs using alternate mAbs or isotopes need to be designed. A humanized and a fully human anti-CD30 mAb are currently being evaluated in phase I/II clinical trials. These mAbs could engage the human immune system against the HL and are capable of directly inducing apoptosis of H-RS cells. In addition, these mAbs could be combined with conventional chemotherapy and are thus promising candidates for further development for the therapy of HL.