After contracting coccidioidomycosis, persons with impaired cellular immunity are more likely than healthy persons to have severe infection, disseminated infection, and higher mortality rates. In this brief review, we summarize the clinical manifestations, diagnosis, treatment, and prevention of coccidioidomycosis in persons infected with human immunodeficiency virus (HIV), recipients of solid organ or hematopoietic stem cell transplants, and recipients of biologic response modifiers. Among individuals infected with HIV, a diagnosis of acquired immunodeficiency syndrome (AIDS) and a CD4 T-lymphocyte count <250 cells/μl were associated with more severe coccidioidomycosis, whereas less severe disease occurred among those with undetectable HIV-RNA and higher CD4 T-lymphocyte counts, indicating that controlled HIV viremia and improved cellular immune status are important in limiting disease. For transplant recipients whose immunosuppression typically peaks in the first 3 to 6 months and tapers thereafter, the greatest risk of acute coccidioidomycosis occurs 6 to 12 months after transplantation. Relapses of recent coccidioidomycosis may occur during ongoing immunosuppression when patients are not taking suppressive antifungal medication. Recipients of biologic agents, especially those that impair tumor necrosis factor α (TNF-α), may be at increased risk for poorly controlled coccidioidomycosis; however, the best way to prevent and treat such infections has yet to be defined.