Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia.