The introduction of biological disease-modifying drugs (DMARDs) has substantially improved the treatment options for patients with rheumatoid arthritis. However, infectious complications represent the most common side effects of these drugs, including severe infections as well as rare opportunistic infections. Treating patients on biological DMARDs is therefore one of the biggest challenges in rheumatology care. The present review describes the current state of knowledge regarding frequency and type of infectious complications associated with biological DMARDs. The article focuses mainly on risk management, in particular on diagnosis and recurrence prevention of tuberculosis and reactivation of hepatitis B virus infection. Furthermore, we discuss the importance of vaccinations in primary disease prevention in patients with rheumatoid arthritis.