Overall, pharmacokinetic (PK) data on the optimal treatment of tuberculosis (TB) patients with moxifloxacin (MFX) are limited, and data on cerebrospinal fluid (CSF) penetration in humans have not been published. We monitored plasma and CSF MFX concentrations over time to optimize treatment in a 31-year-old man with miliary TB and central nervous system involvement (nonactive tuberculous meningitis, cerebral tuberculoma, cervical spinal cord tuberculoma) who could not tolerate isoniazid (INH). Steady-state concentrations were measured after oral doses of 400 and 800 mg once daily. PK parameters were assessed using a validated high-performance liquid chromatography method, and drug susceptibility testing was performed. Results showed MFX concentrations in CSF increased with dose but not proportionally, with AUCCSF/AUCplasma ratios of 0.94 (400 mg) and 0.74 (800 mg). The MFX minimum inhibitory concentration (MIC) against the patient's Mycobacterium tuberculosis isolate was 0.150 mg/liter, and AUC0-24/MIC ratios were adequate in both plasma (59.3 for 400 mg, 129.3 for 800 mg) and CSF (56.0 for 400 mg, 95.3 for 800 mg). High-dose MFX was safe, with no QT prolongation on electrocardiogram and normal renal/liver function. This is the first report of combined CSF and plasma MFX concentrations in a patient with TB and central nervous system involvement. Adequate MFX concentrations were achieved in both plasma and CSF, suggesting MFX can be used for TB with central nervous system involvement if standard treatment is insufficient or poorly tolerated, though therapeutic drug monitoring may be warranted in patients with interacting comedication or high MIC.