Biological agents such as monoclonal antibodies and fusion proteins are widely used for the treatment of patients with various rheumatic disorders, influencing the quality of life, disability and even mortality in patients. However, biological agents can evoke adverse reactions of different grades of severity. Although drug avoidance remains a gold standard in the care of patients hypersensitive to medication, in certain clinical situations the culprit drug is the drug of choice and cannot be replaced by another equally effective compound. In such cases, desensitization can allow the patient to be treated within current guidelines and with the most effective treatment. The authors searched Medline and Scopus databases for English-language sources using the following key words: hypersensitivity, desensitization, biologicals, adalimumab, etanercept, adalimumab, certolizumab, golimumab, rituximab, infliximab, ixekizumab, tocilizumab, anakinra and canakinumab. The aim of our review is to present the current knowledge about desensitization to biological agents and some guidelines according to patient inclusion, contraindications, procedures, and safety requirements. Drug desensitization is a new issue in rheumatology, and the solution to the problem of allergic reactions to biological drugs, which gives patients with rheumatic diseases the opportunity to extend and prolong their therapy. The present article is one of the first widely discussing this topic in the biological treatment of rheumatic diseases.