The first biological drugs in the form of medicinal plant and animal parts have known mankind for millennia. Today, biological medicines are primarily seen as modern biological medicines, which represent the future and are an increasing, important and rapidly evolving topic. Human health, as the most important component of quality of life and the development of medicines required, is not self-evident, but long and complicated. In the case of biological medicinal products, due to the origin and method of production, the most reported is immunogenicity, the detection of which is based on antibodies against the medicinal product (ADA). Biological medicines, like classical medicines, are divided into originators and similars, but the difference between them has a significant impact on the selection and course of treatment. Treatment with immunomodulatory medicinal products is also commonly used with biological medicinal products. The purpose was to review the literature, to produce a systematic, critical review and meta-analysis on the basis of research published so far which covered as much as possible the immunogenicity of biological medicinal products. Specifically, the formation of antibodies against the drug in similar and innovative biological medicinal drugs, their comparison and the possible effect of the use of concomitant therapy with immunomodulators. The research was found with PubMed interface in the MEDLINE database, where we found a wide range of 6684 articles with a predefined search profile. Using the appropriate methodology and PRISMA diagram, we narrowed the set to 51 articles that were included in the meta-analysis and 83 that were analyzed as systematic and critical review. Meta-analysis was performed with Review Manager 5.4. based on the dichotomy split of the highest incidence of positive ADA measurements and taking into account the value of risk ratios with tree chart display. The results of the meta-analysis in three active substances indicate a greater benefit of biosimilars but with different certainties. Other groups, with the exception of two that suggest the benefit of innovative biological medicines, demonstrate the equivalence of biosimilar and originator in the field of immunogenicity. The results in cases of concomitant use of immunmodulators indicate the inability of a statistically significant conclusion. There are also some interesting contradictions with already known foreign findings. Rare emphasis on the assessment and impact of ADA-based immunogenicity in a number of expert articles suggests the need for more adequate demonstration of immunogenicity.