B-cell depletion with rituximab has become a reasonable option for thrombocytopenic purpura (ITP) patients who are refractory for corticosteroids and/or splenectomy, with a response rate of about 55%. The side effects are mostly mild and easily manageable. Long lasting responses are likely in patients who achieve normal platelet counts. The mechanism of action of rituximab in immune-mediated disease in general and ITP in particular is not completely clear. Most probably, depletion of the memory B-cell compartment causes a decrease in autoantibody formation. To date it is impossible to predict the response to rituximab, although the presence of a high affinity Fc receptor for IgG seems to have positive predictive value. Future studies will have to clarify these issues, as well as possible effects of repeated rituximab treatment on primary and secondary immune responses. Pediatr Blood Cancer 2006;47:703–705. © 2006 Wiley-Liss, Inc.