Fungi are ubiquitous commensals, seasoned predators, and important agents of emerging infectious diseases [1]. The immune system assumes the essential responsibility for responding intelligently to the presence of known and novel fungi to maintain host health. In this Review, we describe the immune responses to pathogenic fungi and the varied array of fungal agents confronting the vertebrate host within the broader context of fungal and animal evolution. We provide an overview of the mechanistic details of innate and adaptive antifungal immune responses, as well as ways in which these basic mechanisms support the development of vaccines and immunotherapies.