Paracoccidioidomycosis (PCM) is an endemic mycosis found in Latin America that causes systemic disease mostly in immunocompetent hosts. A small percentage of PCM occurs in immunocompromised patients where low clinical suspicion of the infection, late diagnosis, and uncertainties about its management are factors that negatively impact their outcomes. We conducted a literature review searching reports on PCM associated to HIV, cancer, maligned hemopathies, solid organ transplantation, and immunotherapies, in order to check for peculiarities in terms of natural history and challenges in the clinical management of PCM in this population. HIV patients with PCM usually had low T CD4+ cell counts, pulmonary and lymph nodes involvement, and a poorer prognosis (≈50% mortality). Most of the patients with PCM and cancer had carcinoma of the respiratory tract. Among maligned hemopathies, PCM was more often related to lymphoma. In general, PCM prognosis in patients with malignant diseases was related to the cancer stage. PCM in transplant recipients was mostly associated with the late phase of kidney transplantation, with a high mortality rate (44%). Despite being uncommon, reactivation of latent PCM may take place in the setting of immunocompromised patients exhibiting clinical particularities and it carries higher mortality rates than normal hosts.