Pseudallescheria boydii and its asexual form, Scedosporium apiospermum, are ubiquitous, saprophytic fungi that commonly cause cutaneous infection. However, in certain circumstances, P. boydii can also cause invasive disease, which can involve the central nervous system (CNS). When the CNS becomes involved, treatment is difficult, therapeutic options are limited, and the prognosis is poor. We report a case of Pseudallescheria brain abscess successfully treated with surgical drainage and systemic voriconazole, the first such case to be described in the literature. We also review previously reported cases of CNS pseudallescheriasis and evaluate therapeutic options.