Cerebral blastomycosis is a rarely reported disease. We report three cases of cerebral blastomycosis previously treated with standard antifungal therapy, which were subsequently successfully treated with voriconazole. The first is a 29-year-old man who initially presented with concomitant cutaneous and osseous blastomycosis; the second is a 50-year-old man who initially presented with prostatic, pulmonary and cutaneous lesions. The third patient was a 63-year-old man who presented with hemiplegia and multiple intra-cerebral blastomycomas. This report represents the first two documented relapses, in Canada, of CNS blastomycosis following treatment with itraconazole and, to our knowledge, among the first three worldwide human cases of cerebral blastomycosis treated successfully with voriconazole.