Over one million people in The Netherlands are estimated having an immunodeficiency, of which the majority has an acquired immunodeficiency due to immunosuppressive medication. These patients are at risk for a more severe course of common infections, and also for opportunistic infections and viral reactivations. The following topics are discussed: types of immunodeficiency and how to estimate its severity; commonly seen infections in immunocompromised patients; recommended screening before start of immunosuppressive medication; pitfalls in clinical clues and diagnostics, and safety and immunogenicity of vaccination in these patients. Conclusively, recognition of an immunodeficiency and awareness of the risks and preventive measures are required. This article attempts to provide a pragmatic classification on the infection risk per type of immunosuppressive medication for clinical practice.