Patients with long-standing chromoblastomycosis may respond poorly to standard treatments such as amphotericin B, oral antifungals, surgical measures or thermotherapy. The objective of this study was to determine the potential of alternate week and combination therapy with itraconazole and terbinafine in the treatment of poorly responsive, or non-responsive, chromoblastomycosis. Four patients with longstanding chromoblastomycosis (8-23 years) caused by Fonsecaea pedrosoi had responded poorly to standard therapies including monotherapy with the oral antifungal agents. In order to try and improve the response to oral itraconazole and terbinafine, alternate week or combination therapy with itraconazole and terbinafine was initiated. Bloodwork including complete blood count and liver function tests were performed every 3-8 weeks to ensure patient safety. Reduction or resolution of lesions of chromoblastomycosis was noted with alternate week or combination treatment using oral itraconazole and terbinafine. Three of four patients experienced no clinical side-effects; the third reported mild, transient gastric discomfort which responded to antacids. Bloodwork generally remained within normal limits throughout the entire course of treatment with no clinically significant changes. The combination therapy was considered effective in treating the poorly responsive chromoblastomycosis of all four patients. Some success with alternative week therapy was also noted in one patient. The favorable response and lack of significant adverse effects suggests that these regimens may be an option for some patients with chromoblastomycosis.