Antibiotic prophylaxis is one of the mainstays of therapy of primary immunodeficiencies. We aim to summarize what is known about antibiotic prophylaxis for select primary immunodeficiencies.In recent years, there has been a push towards more evidence-based practices for antimicrobial prophylaxis for many conditions such as antifungal prophylaxis for extremely premature neonates and antibiotic prophylaxis for neutropenia associated with chemotherapy. However, there are remarkably few data regarding antibiotic prophylaxis in primary immunodeficiencies and regimens vary greatly between practices.Currently, antibiotic prophylaxis is guided by the common microbial pathogens seen in specific immunodeficiencies, and experience with other chronic illnesses such as cystic fibrosis, HIV, and immunosuppression from transplantation. Controlled studies are necessary to address the preferred antimicrobial and immunomodulator regimens for most of the primary immunodeficiencies.