Nocardiosis is an opportunistic infection that often occurs in patients who are in an immunosuppressive state. It is often difficult to treat and the mortality is high. We report on an immunocompromised patient who suffered from cerebral nocardiosis with multiple brain abscesses which was successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) for a period of 6 months. The resolution of the brain abscesses with this treatment was documented by serial CT scans. Our experience indicates that a short course of TMP-SMX in a low dose may not be effective in preventing the spread of nocardiosis to the central nervous system (CNS). We recommend a prolonged course of a high dose of TMP-SMX in the treatment of CNS nocardiosis.