Pneumocystis pneumonia (PCP) can be life threatening for children receiving chemotherapy and immunosuppressive medication, including high-dose steroids. Although there are no current guidelines for prophylaxis in pediatric oncology patients, ongoing studies are evaluating the efficacy, side effects, ease of administration, and compliance of drugs used for PCP prophylaxis. Drugs currently being prescribed in practice include Bactrim, pentamidine, dapsone, and atovaquone. Bactrim remains superior for preventing PCP, but alternatives are being analyzed and investigated for those unable to tolerate Bactrim because of drug allergy or side effects. Educating patients and families about the importance of PCP prophylaxis and compliance should be a priority for all health care providers caring for children receiving immunosuppressive medications, including chemotherapy.