Recent shifts in the epidemiology of invasive fungal infections (IFIs) among transplant and oncology populations have led to new recommendations on treatment; however, they have also brought new controversies. New pharmacologic therapies are being studied and guidelines for management of several IFIs have been changed accordingly. More information is being discovered about unique genetic factors that put some transplant recipients at greater risk than others for fungal infection. The role of immunomodulation continues to be investigated, and the delicate balance of maintaining some immune integrity while assuring protection of the graft remains critical. For transplant and oncology patients, the diagnosis and management of IFIs remain challenging, and improving outcomes depends on continued progress in all of these arenas. This article highlights recent advances and important factors to consider when treating transplant and oncology patients with IFIs.