Loss of exclusivity for biological therapeutics opens the door for biosimilar development. Biosimilars must demonstrate structural, functional, and clinical similarity with a currently approved biological originator product. A therapeutic alternative for biologic-naive patients, a single switch from an originator to biosimilar has also been studied in clinically stable patients; further, switching therapy multiple times (alternating) between an originator and a biosimilar has been investigated. Because biosimilars are not identical to originators and no robust clinical data have convincingly demonstrated that switching or alternating therapy of stable patients is safe and efficacious, there is an imperative need to understand the characteristics of well-designed clinical trials to support these practices. Areas covered: Clinical trials of biosimilars are reviewed, with an emphasis on trial designs that incorporate therapy switching, including the NOR-SWITCH study as an example. Expert opinion: As currently designed, biosimilar clinical trials provide insufficient information to support switching or alternating between originator products and their biosimilars. Lack of regulatory guidance contributes to this void. More robust data are required to inform the safety and efficacy of switching or alternating therapies, particularly regarding immunogenicity risks. Studies that also include alternations of therapy are needed to address these knowledge gaps.