Biosimilars are biologically derived products that are highly similar to reference medicinal products (RPs) but not identical. They are developed to provide comparable safety, quality, and efficacy to RPs, but they are not generic substitutes. The development of biosimilars involves a rigorous process, including analytical, functional, and nonclinical evaluations, as well as clinical trials to confirm similarity in efficacy, safety, and immunogenicity. Despite their value, biosimilars face controversies regarding immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The approval of biosimilars stimulates market competition, enhances healthcare sustainability, and improves patient access. However, maximizing their benefits requires collaboration between regulators and developers to ensure quality, safety, and efficacy. This review discusses the regulatory and manufacturing requirements for biosimilars, providing insights for informed prescribing. It also addresses the post-marketing safety monitoring of biosimilars and the main controversies in their use. The review highlights the differences between biosimilars and other biologics, such as intended copies, biobetters, and standalone biologics. It emphasizes the importance of rigorous comparability studies to ensure biosimilars are safe and effective. The review also discusses the challenges in developing biosimilars, including the need for extensive analytical testing, the impact of post-translational modifications, and the importance of clinical trials to confirm similarity. The review concludes that biosimilars are a valuable alternative to RPs, but their successful implementation requires careful consideration of regulatory, manufacturing, and clinical factors.Biosimilars are biologically derived products that are highly similar to reference medicinal products (RPs) but not identical. They are developed to provide comparable safety, quality, and efficacy to RPs, but they are not generic substitutes. The development of biosimilars involves a rigorous process, including analytical, functional, and nonclinical evaluations, as well as clinical trials to confirm similarity in efficacy, safety, and immunogenicity. Despite their value, biosimilars face controversies regarding immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The approval of biosimilars stimulates market competition, enhances healthcare sustainability, and improves patient access. However, maximizing their benefits requires collaboration between regulators and developers to ensure quality, safety, and efficacy. This review discusses the regulatory and manufacturing requirements for biosimilars, providing insights for informed prescribing. It also addresses the post-marketing safety monitoring of biosimilars and the main controversies in their use. The review highlights the differences between biosimilars and other biologics, such as intended copies, biobetters, and standalone biologics. It emphasizes the importance of rigorous comparability studies to ensure biosimilars are safe and effective. The review also discusses the challenges in developing biosimilars, including the need for extensive analytical testing, the impact of post-translational modifications, and the importance of clinical trials to confirm similarity. The review concludes that biosimilars are a valuable alternative to RPs, but their successful implementation requires careful consideration of regulatory, manufacturing, and clinical factors.