Antiphospholipid syndrome (APS) and catastrophic antiphospholipid syndrome (CAPS) can be challenging to treat. As they are rare, clinicians are not often exposed to these complex diseases. For the patient resistant to standard treatments new therapeutic directions can be perplexing, especially in the context of ongoing thromboses and bleeding episodes. We describe 3 patients, 2 with APS and one with CAPS, resistant to conventional medications, who responded to treatment with rituximab, an anti-CD20 monoclonal antibody. Since rituximab infusion, all the patients have had stable platelet counts and no further episodes of bleeding or thromboses.