Invasive fungal infections are an increasingly important cause of morbidity and mortality. We provide a summary of important changes in the epidemiology of invasive fungal infections, citing examples of new emerging pathogens, expanding populations who are at-risk, and increasing antifungal resistance. We review how human activity and climate change may play a role in some of these changes. Finally, we discuss how these changes create the need for advances in fungal diagnostics. The limitations of existing fungal diagnostic testing emphasize the critically important role of histopathology in the early recognition of fungal disease.