Fungal infections represent a significant global public health concern, causing over 1.6 million deaths annually and substantial morbidity, particularly among immunocompromised individuals. In this context, primary and secondary immunodeficiencies play a critical role in developing invasive mycoses caused by opportunistic fungi. This chapter explores how various types of immunodeficiency compromise host defense mechanisms and promote the dissemination of fungal pathogens. Several primary immunodeficiencies are described, including chronic granulomatous disease, CARD9, IL-12, and MALT1 deficiencies, DOCK8 deficiency, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and mutations in IKBKB, all associated with increased susceptibility to infections by Candida, Aspergillus, Cryptococcus, among other fungal species. Secondary immunodeficiencies, commonly encountered in clinical settings, are also reviewed, such as malnutrition, diabetes mellitus, chronic kidney disease (uremia), HIV infection, coronavirus disease 2019 (COVID-19), and organ transplantation, all of which predispose individuals to severe fungal infections. Key etiological agents, including Candida, Aspergillus, Histoplasma, Cryptococcus, Pneumocystis, Paracoccidioides, and Mucor, are discussed in terms of their clinical manifestations, incidence, and risk factors in the context of immunosuppression.