Dimorphic endemic fungi exist as mold and yeast forms at room and body temperature within the host, respectively. Primary infection can arise from new environmental exposure and less frequently through organ transplantation. Reactivation of latent infection can occur when immunosuppression is introduced or intensified. Transplant and immunocompromised hosts (ICH) represent important populations at risk for complicated and disseminated forms of endemic mycoses (EM). Diagnosis is challenging as immunosuppression contributes to insidious clinical presentations resulting in diagnostic and treatment delays. Herein, we present updated diagnosis and prevention strategies for EM in the potential organ donor, transplant candidate and recipient, and ICH. Several EM have previously been considered as restricted to a limited geographical area; however, factors such as global warming, changing precipitation patterns, and increased travel are actively expanding the geographical distribution of endemic fungi. Serological testing, often used in the immunocompetent host, has significant limitations in transplant recipients and ICH. Fungal molecular methods have emerged as an important complementary diagnostic strategy for EM but would benefit from greater standardization and wider availability. High clinical suspicion and a multipronged diagnostic approach are recommended for timely diagnosis and prevention of complications. In ICH, combining diagnostic methods increases diagnostic yield for EM. Immunosuppression-specific risk assessment, laboratory monitoring, and targeted antifungal prophylaxis are pivotal to reduce EM burden. The use of molecular methods for early diagnosis and the role of newer azoles and immunomodulation in the management of EM require further investigation.