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Bacterial infections frequently occur within or near the vascular network as the vascular network connects organ systems and is essential in delivering and removing blood, essential nutrients, and waste products to and from organs. In turn, the vasculature plays a key role in the host immune response to bacterial infections. Technological advancements in microfluidic device design and development have yielded increasingly sophisticated and physiologically relevant models of the vasculature including vasculature-on-a-chip and organ-on-a-chip models. This review aims to highlight advancements in microfluidic device development that have enabled studies of the vascular response to bacteria and bacterial-derived molecules at or near the vascular interface. In the first section of this review, we discuss the use of parallel plate flow chambers and flow cells in studies of bacterial adhesion to the vasculature. We then highlight microfluidic models of the vasculature that have been utilized to study bacteria and bacterial-derived molecules at or near the vascular interface. Next, we review organ-on-a-chip models inclusive of the vasculature and pathogenic bacteria or bacterial-derived molecules that stimulate an inflammatory response within the model system. Finally, we provide recommendations for future research in advancing the understanding of host–bacteria interactions and responses during infections as well as in developing innovative antimicrobials for preventing and treating bacterial infections that capitalize on technological advancements in microfluidic device design and development.