Central nervous system, affliction, although rare, represents one of the most severe extra-pulmonary manifestations of tuberculosis, potentially leading to substantial morbidity and mortality if not promptly addressed. Cranial tuberculosis can manifest in various forms, including tuberculomas, encephalitis, abscesses, and meningitis, with the latter being the most critical and carrying a poor prognosis if left untreated. Spinal tuberculosis, accounting for approximately 50% of musculoskeletal TB cases, can present with a spectrum of symptoms, ranging from simple back pain to more severe neurological deficits such as weakness and deformity. Anti-tuberculosis medications remain the cornerstone of treatment, and this Element offers an algorithmic approach to managing referrals of suspected tuberculosis, incorporating pertinent clinical information to facilitate effective decision-making.