This chapter discusses the current management of cryptococcal meningoencephalitis in terms of antifungal drug therapy, the management of complications, notably raised cerebrospinal fluid (CSF) pressure, the issues of the timing and choice of antiretroviral therapy (ART) in HIV-infected patients, and the management of symptomatic relapse, including immune reconstitution syndromes. The result is that if patients anywhere in the world with access to ART survive the initial critical months of cryptococcal meningoencephalitis, they have an excellent long-term prognosis. The chapter highlights opportunities for improved intervention, including for earlier diagnosis and treatment. The emphasis is on HIV-associated infection in resource-limited settings, which constitute the majority of the global burden of cryptococcal infection. Examination of outcomes of therapy for HIV-associated cryptococcal meningitis in resource-limited settings illustrates that a high proportion of patients with abnormal mental status at presentation is associated with high mortality irrespective of the antifungal treatment available. The chapter also summarizes some of the reasons underlying the high mortality of patients with cryptococcal meningitis, including the constraints on optimal management in developing-country settings.