This chapter will provide an overview of pragmatic trials in the biologic medicines setting. This chapter will start with an introduction to biologic medicines in terms of how they are defined, how they are broadly used in clinical medicine, and types of research questions typically studied in biologics using a pragmatic clinical trial design. A high-level summary of general pharmacovigilance concerns, such as immunogenicity, manufacturing variability, and identification/traceability is provided. Biologic-specific considerations will include topics such as the complexity of patient profiles and treatment. A biologic focus of pragmatic trial designs and their applicability to biologics, common endpoints, and strengths and limitations of real world data sources for pragmatic trials will be described. This chapter will be valuable to researchers and scientists who are interested in understanding considerations for conducting a pragmatic clinical trial of biologic medicines.