Biological agents represent an emerging therapeutic option in current medicine. They are widely used in many clinical conditions including inflammatory and oncologic diseases. Although they are highly efficient in many cases, they also can produce significant adverse immunologic reactions due to hypersensitivity or their own biological activity. Here we present management strategies for hypersensitive reactions induced by biological agents. Skin testing is most common diagnostic tool for drug causality assessment. Desensitization protocols have been found to be safe and effective. Pharmacovigilance system and safety of biologic therapies require further extensive research.