Opportunistic infections affect patients with immunocompromised status and are caused by common microorganisms with more severe presentations, or atypical organisms that do not cause disease in the immunocompetent. The type of infection varies with the type of immune dysfunction. Patients with cell-mediated immune dysfunction tend to be infected with a range of viral infections, intracellular bacteria, and fungi. This contrasts to patients with defects in humoral immunity, where infections with encapsulated bacteria, and enteric organisms such Giardia lamblia and enteroviruses predominate. Patients with phagocytic defects are especially prone to infections with Gram-negative bacteria and fungi, whilst those with complement disorders are prone to recurrent infections with encapsulated bacteria. In contrast to patients with primary immunodeficiencies, which usually present with only one defect of the above, acquired immunodeficiencies present with a variety of those, and clinical presentations are diversified. The epidemic of HIV and AIDS shed some light into infections that were before extremely rare, by making them frequent, but with the advent of anti-retroviral therapy their clinical presentation has shifted. Also, the emergence of novel immunotherapies for cancer and autoimmune diseases, allied with an increase in organ transplant has increased the pool of immunosuppressed patients without HIV, which present differently regarding opportunist infections. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. Our aim was to revise and summarize the most frequent opportunist infections, and how their presentation and course compares in different immunosuppressed diseases (HIV and non-HIV).