Patients with Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are at risk for multiple infectious and oncologic complications. In such cases, Occam's razor need not apply: multiple infections and malignancies are often present concurrently upon presentation to care. A patient off anti-retroviral therapy (ART) for several years developed advanced HIV infection (CD4 count 19 cells/uL) and presented with five simultaneous opportunistic infections including Pneumocystis jiroveci pneumonia (PJP), cytomegalovirus (CMV) retinitis, Mycobacterium avium complex (MAC) bloodstream infection, chronic hepatitis B virus (HBV), and Epstein-Barr virus (EBV) viremia. Simultaneously, he was found to have primary central nervous system (CNS) B-cell lymphoma. Treatment decisions for such patients are often complex, as ideal therapy for one disease may directly counter or interact with therapy for another. For instance, methotrexate for primary CNS lymphoma and trimethoprim/sulfamethoxazole for PJP is a strictly contraindicated medication combination. It is important to understand not just the management of any single opportunistic disease in patients with advanced HIV, but how to balance management for patients with a variety of concurrent processes. In an era when HIV care is becoming increasingly simplified, patients presenting with advanced infection highlight the lack of data on how best to manage patients with multiple concurrent disease processes. Significant further research is needed to clarify ideal comparative therapy.