Data from a number of transplant centers has shown that several intensive therapy regimens, supported by autologous stem cell transplantation, have the capability to produce durable responses in a proportion of patients with Hodgkin's disease progressive after combination chemotherapy. Although many questions regarding the optimal use of autotransplantation remain unanswered, the issue of the preferred timing at which to apply transplantation is of critical importance in planning therapeutic strategies for patients with this disease. This paper will focus on the timing options for autotransplantation in Hodgkin's disease. In the absence of a formal Phase III study comparing conventional salvage therapy versus autotransplantation in first relapse patients, the encouraging results from our center and others support the use of transplantation at the time of first relapse after combination chemotherapy. Non-relapse mortality is low in this setting, and the primary problem has been recurrent disease despite transplantation. Risk factors for both disease recurrence, as well as for the probability of progression-free survival, can be defined based on biologic features present at the time of first relapse after chemotherapy, and may provide a basis for improving the current transplant results for first relapse patients. Prolonged follow-up will be important to define the incidence and risk of late toxicities in autografted patients.