This chapter examines the vital role of the vascular system and the impact of vascular senescence on health. It highlights the importance of vascular integrity and how its aging contributes to several diseases using advanced in vitro systems, such as organ-on-chips, which are introduced as tools to model vascular senescence and study molecular mechanisms and therapeutics testing. The chapter emphasizes the development of a blood–brain barrier in vitro model to improve understanding of brain vascular senescence.