Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g., cell lines), processes, or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic, and clinical assessment for similarity. The goal of the phase 3 clinical development program for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints, and statistical methods. Based on the clinical trials results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practicing clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases. This article is protected by copyright. All rights reserved.