OBJECTIVES:To examine physicians' perceptions of the uptake of biosimilars. DESIGN:Systematic review. DATA SOURCES:MedLine Ovid and Scopus databases at the end of 2018. ELIGIBILITY CRITERIA:Original scientific studies written in English that addressed physicians' perceptions of the uptake of biosimilars. DATA EXTRACTION AND SYNTHESIS:The search resulted in altogether 451 studies and 331 after removing duplicates. Two researchers examined these based on the title, abstract and entire text, resulting in 20 studies. The references in these 20 studies were screened and three further studies were included. The data of these 23 studies were extracted. All the publications were quality assessed by two researchers. RESULTS:Most of the selected studies were conducted in Europe and commonly used short surveys. Physicians' familiarity with biosimilars varied: 49%-76% were familiar with biosimilars while 2%-25% did not know what biosimilars were, the percentages varying from study to study. Their measured knowledge was generally more limited compared with their self-assessed knowledge. Physicians' perceptions of biosimilars also varied: 54%-94% were confident prescribing biosimilars, while 65%-67% had concerns regarding these medicines. Physicians seemed to prefer originator products to biosimilars and prescribed biosimilars mainly for biologic-naive patients. They considered cost savings and the lower price compared with the originator biologic medicine as the main advantages of biosimilars, while their doubts were often related to safety, efficacy and immunogenicity. 64%-95% of physicians had negative perceptions of pharmacist-led substitution of biologic medicines. CONCLUSIONS:Physicians' knowledge of and attitudes towards biosimilars vary. Although physicians had positive attitudes towards biosimilars, prescribing was limited, especially for patients already being treated with biologic medicines. Perceptions of pharmacist-led substitution of biologic medicines were often negative. Education and national recommendations for switching and substitution of biologic medicines are needed to support the uptake of biosimilars.