The article reviews the roles of endothelial cells and macrophages in the central nervous system (CNS), highlighting their interactions and contributions to various physiological and pathological processes. Endothelial cells form the blood-brain barrier (BBB) and play a crucial role in maintaining the CNS's homeostasis. Macrophages, including microglia and perivascular macrophages (PvMΦ), are key players in regulating vascular integrity, blood flow, and neuroinflammation. Recent studies have revealed that these cells share common developmental origins and interact closely in the CNS. Microglia and endothelial cells influence each other's polarization and activation states, and their interactions are critical for maintaining the BBB and regulating vascular remodeling. Macrophages modulate cerebral blood flow (CBF) and contribute to neurovascular coupling, while also influencing angiogenesis and endothelial cell viability. PvMΦs are involved in long-term vascular remodeling and phagocytosis of waste products, potentially affecting the BBB and fluid dynamics in the brain. The article also discusses the impact of macrophages on perivascular deposits, such as iron and calcifications, and their role in neurodegenerative diseases. Overall, the interplay between endothelial cells and macrophages is essential for maintaining brain health and is implicated in various CNS disorders.The article reviews the roles of endothelial cells and macrophages in the central nervous system (CNS), highlighting their interactions and contributions to various physiological and pathological processes. Endothelial cells form the blood-brain barrier (BBB) and play a crucial role in maintaining the CNS's homeostasis. Macrophages, including microglia and perivascular macrophages (PvMΦ), are key players in regulating vascular integrity, blood flow, and neuroinflammation. Recent studies have revealed that these cells share common developmental origins and interact closely in the CNS. Microglia and endothelial cells influence each other's polarization and activation states, and their interactions are critical for maintaining the BBB and regulating vascular remodeling. Macrophages modulate cerebral blood flow (CBF) and contribute to neurovascular coupling, while also influencing angiogenesis and endothelial cell viability. PvMΦs are involved in long-term vascular remodeling and phagocytosis of waste products, potentially affecting the BBB and fluid dynamics in the brain. The article also discusses the impact of macrophages on perivascular deposits, such as iron and calcifications, and their role in neurodegenerative diseases. Overall, the interplay between endothelial cells and macrophages is essential for maintaining brain health and is implicated in various CNS disorders.