Pharmacovigilance encompasses the science and activities focused on the detection, assessment, understanding, and prevention of drug adverse effects or any other drug-related problem. Well-established pharmacovigilance system and the implementation of good pharmacovigilance practices are associated with the continuous evaluation of risk/benefit ratio of medicines. In recent years, the availability of biologics and biosimilar drugs has increased significantly, and guaranteeing the safe and effective use of these medical products through routine pharmacovigilance activities has become a complex challenge. Biologics include various products with active substances obtained by living cells or organisms, produced by complex biotechnological processes. Post-marketing surveillance is crucial for biologics, including biosimilars, due to their multifaceted structures and intricate manufacturing processes involving numerous upstream and downstream steps that might lead to variability and increased potential for immunogenicity. Additionally, biologics are often used in patients with chronic or severe diseases, are highly sensitive to environmental factors, and exhibit specific distribution characteristics. The acceptable variations between reference biologics and biosimilars can lead to rare or delayed safety events, like immunogenicity that are often detectable only in larger, more diverse patient populations during real-world clinical practice. Moreover, the abbreviated application for safety and efficacy of biosimilars, in comparison to large clinical trial program needed for the reference product, enrages the role of post-marketing surveillance and pharmacovigilance. Enhancing the traceability of biologics by educating reporters will improve the quality of reporting and signal detection. This, in turn, will facilitate the timely implementation of risk minimization measures, resulting in improve patient safety and public health.