Discovered more than 100 years ago as a human pathogen, the Cryptococcusneoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence inits association with clinical disease in the last 30 years. First isolated in fermenting peach juice, andidentified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogenhas now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized asan opportunistic infection and was first noted to be associated with reticuloendothelial cancers inthe 1950s. Since then, advances in transplant immunology, medical science and surgical techniqueshave led to increasing numbers of solid organ transplantations (SOT) and hematological stem celltransplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally,however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic,particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease,environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis.