Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune-mediated non-malignant hematologic disorders, with infection being the most common non-hematological adverse event from these therapies. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection, including opportunistic infections. Screening and antimicrobial prophylaxis against tuberculosis, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia, are indicated in selected patients on steroids and with certain risk factors for infection. Rituximab is associated with hepatitis B virus reactivation. All patients planned to be started on rituximab should be screened for hepatitis B surface antigen and total core antibody, with antiviral prophylaxis given depending on test results. In eculizumab treated patients, immunization against meningococcal serogroups ACWY and B is recommended. In addition, some guidelines suggest antibiotic prophylaxis for the duration of eculizumab treatment. In splenectomized patients, counseling and immunization are cornerstones of infection prevention. Several federal and society guidelines about immunizations and prophylactic antimicrobial therapies for patients treated with various immunosuppressive agents exist and are summarized in this manuscript in a clinical-focused table. In addition, management suggestions are made where no formal guidelines exist. 2 | PATIENT COUNSELING An important part of infectious disease prevention in immunocompromised patients entails the education of the patient, family, and friends. Household and other close contacts of persons with altered immunocompetence should be educated in hand hygiene and avoid contact with the patient when they are experiencing an infectious process. 12 Proper food and water hygiene measures are important to prevent