We present a Peruvian human immunodeficiency virus (HIV)-positive patient receiving first-line therapy for tuberculosis who presents with neurological complications to highlight some of the major issues in the diagnosis and management of human immunodeficiency virus-related central nervous system complications in resource-poor settings. These include limited options for diagnosing extrapulmonary and drug-resistant tuberculosis; the importance of central nervous system. imaging; and the management conundrum when faced with a broad differential diagnosis. This patient waswith drug-resistant tuberculosis of the brain, unmasked by immunologic recovery in the setting of recent initiation of antiretroviral treatment. We argue that aggressive and timely empiric multidrug-resistant tuberculosis treatment is important in cases where drug-resistant tuberculosis is suspected. Knowledge gaps include a limited understanding of immune reconstitution and the optimal timing of antiretroviral treatment in the setting of drug-resistant tuberculosis. © 2008 Sage Publications.