Although the incidence of HIV-associated cryptococcosis has decreased in developed countries since the introduction of antiretroviral therapy, this disease continues to cause significant morbidity and mortality in sub-Saharan Africa among patients with AIDS. Important strides have been made in an attempt to decrease the burden of disease, particularly the development of the lateral flow assay cryptococcal antigen (LFA CrAg) as a diagnostic tool in resource-limited settings, coupled with the introduction of pre-emptive treatment with fluconazole for HIV-positive patients at risk for cryptococcosis with a positive LFA CrAg. Among solid organ transplant recipients, recent prospective studies have identified cryptococcosis as the third most common invasive fungal infection, and progress is being made toward earlier diagnosis and more effective therapy. Finally, the Cryptococcus gattii outbreak in British Columbia, Canada and the US Pacific Northwest is providing important new insights into the emergence of this pathogen in geographic areas previously considered low risk for acquisition of infection. Understanding the similarities and differences among C. gattii and C. neoformans infections will provide critical insights into the behavior of these organisms in the human host. Both pathogens affect immunocompetent and immunosuppressed hosts, causing pulmonary, central nervous system and widely disseminated infections. Treatment recommendations in the future will necessarily take into account the site of infection, clinical severity of the infection, Cryptococcus species, host immune status and economic resources.