Despite improved therapies for human immunodeficiency virus and central nervous system cryptococcal infection, early mortality from human immunodeficiency virus-related cryptococcal meningitis remains unchanged. Unrecognized cerebral infarction may be a contributing factor. We believe that serial imaging with higher resolution techniques will lead to increased diagnosis of this often fatal condition. Further studies on adjunctive therapies and the optimal timing of antiretroviral therapy are also needed to improve outcomes in acquired immunodeficiency syndrome-associated cryptococcal meningitis. © 2010 Lippincott Williams & Wilkins.