Background: In the US, a new approval pathway for biosimilars has been established as part of the Aff ordable Care Act. Biosimilars are anticipated to increase treatment options and lower the growth in spending on biologicals. How the commercial prospects for biosimilars will play out in the US is uncertain. From a regulatory, approvals, and market standpoint, Europe is ahead of the US with respect to biosimilars. Lessons may be drawn from European experience. Objective: To examine challenges and opportunities with respect to market uptake of biosimilars in the US. Methods: We reviewed Medline-indexed manuscripts and grey literature published in the past fi ve years on the topics of biosimilar development and market uptake. The data collected in this review informed the development of two stakeholder surveys for payers and physicians. Main Survey Results: Almost all physicians surveyed believe that if a biosimilar is approved by the US Food and Drug Administration (FDA), the product will perform similarly to the originator biological with regard to safety and effi cacy. Most physicians say they will likely prescribe biosimilars as soon as they are approved by FDA. Additionally, the majority of physicians feel comfortable switching an existing patient from the originator biological to a biosimilar. All payer respondents intend to promote biosimilar uptake by diff erentiating between the originator biological and biosimilar through the use of formulary tiering to steer patients and physicians towards biosimilars. Most payers said they would recommend therapeutic switching of biosimilars. Seventy-fi ve per cent of payer respondents expect biosimilars to have a 15-35% price discount. Discussion: Physicians will display caution when deciding on prescribing biosimilars to existing patients. Payers will look to regulatory authority guidance for further support. To maximize cost savings, payers will likely employ formulary management tools, such as higher cost sharing for originators and lower cost sharing for biosimilars. To ensure access to and monitoring of post-marketing safety and eff ectiveness of biosimilars, payers may establish patient registries through coverage with evidence development arrangements. The expected price discount of 15-35% for biosimilars is not large. Furthermore, higher rebates on originator biologicals may be used by manufacturers as a barrier to adopting biosimilars. Therefore, biosimilar manufacturers will likely have to treat biosimilars as any other branded product. Finally, biosimilars will be subject to competition from new biologicals in the same therapeutic class, including incremental improvements to existing originators.