Cryptococcus gattii is a species that has received more recognition in the recent past as distinct from Cryptococcus neoformans. C gattii is known to cause meningeal disease in both immunocompetent and immunosuppressed hosts. Patients may be clinically asymptomatic until immunosuppressive conditions occur such as corticosteroid treatment or an HIV infection. HIV-associated cryptococcal infections are most often due to C neoformans. C gattii is found in a minority. Speciation and subtyping of Cryptococcus are not always accomplished. In many parts of the world, there is no availability for speciation of Cryptococcus. Travel history may provide a clue to the most probable species. This case demonstrates a case of C gattii meningitis with a multiplicity of complications. These include advanced HIV disease secondary to nonadherence, immune reconstitution inflammatory syndrome, and superior sagittal sinus thrombosis. The patient represented diagnostic and therapeutic dilemmas over time. Headache was the primary symptom in cryptococcal meningitis, immune reconstitution inflammatory syndrome, and superior sagittal sinus thrombosis. All are discussed in detail as potential etiologies for the primary disease. Isavuconazonium is a relatively new broad-spectrum antifungal azole that was used as salvage therapy.