Churg-Strauss syndrome (CSS) is characterized by small-vessel vasculitis, extravascular granulomatous inflammation, and massive eosinophilia in tissues and blood, and is often accompanied by a history of preclinical asthma and/or allergic rhinitis lasting several years before the syndrome develops its full clinical picture. Corticosteroids, often in combination with cytotoxic agents, comprise standard therapy; however, a number of patients appear to be resistant to treatment and there is a need for more effective regimens. B cell depletion may be an effective treatment option for CSS. Here, we describe two patients resistant to conventional therapy who were treated with rituximab and experienced a rapid and substantial decrease in disease activity and asthmatic symptoms and an increase in physical capacity.