Fungi are found in virtually every environment, and comprise a significant portion of the normal microflora of healthy individuals. Some species of fungi are aeroallergen sources capable of inducing sensitization and causing exacerbation of asthma and respiratory allergy. Others are transmissible between hosts and may cause no symptoms in healthy individuals. However, immune suppressed individuals may develop invasive disease marked by tissue invasion with a potential for widespread dissemination. Existing therapies for patients consist of antifungal drugs, yet these require prolonged administration with the possibility of adverse side effects, and may be rendered ineffective by the emergence of antifungal-resistant strains. It is therefore of interest to increase our understanding of host-pathogen interactions in order to facilitate the development of new therapies for individuals suffering from fungal infection and disease. These early interactions are shaped by an array of constituent and secreted factors that stimulate or inhibit host immune responses toward protective or detrimental immunity. Likewise, an array of preformed factors and tissue-resident cells provide early protection from fungal infection and provide extracellular signals that result in localized recruitment of inflammatory cells and determine the character of subsequent adaptive antifungal immunity. This Research Topic explores the host and fungal pathways that program innate and adaptive immunity and the immune cells, molecules, and regulatory pathways that comprise protective or detrimental responses to fungal exposure or infection. Over 200 authors contributed reviews, opinions, or original research focusing on antifungal immunity in humans and in experimental models. We believe that the results of these efforts provide a benchmark for further advances and improved antifungal therapies.