The blood-brain barrier (BBB) is a highly regulated structure composed of endothelial cells, pericytes, and astrocytes, which selectively prevents the entry of substances from the peripheral blood into the central nervous system (CNS). The BBB also interacts with perivascular macrophages (MΦs) and microglia, which play crucial roles in modulating the activation state of BBB components and themselves. Alterations in systemic metabolic and inflammatory states can lead to endothelial dysfunction, reducing BBB integrity and potentially allowing peripheral blood factors to leak into the CNS, triggering neuroinflammation. This review explores the intricate relationship between microglia and the BBB in health and disease, highlighting the importance of understanding these interactions for developing novel therapeutic strategies for neurological conditions involving immune and vascular mechanisms. Key topics include the functional roles of microglia, their interactions with the BBB, and their involvement in conditions such as stroke, diabetes, and systemic inflammation.The blood-brain barrier (BBB) is a highly regulated structure composed of endothelial cells, pericytes, and astrocytes, which selectively prevents the entry of substances from the peripheral blood into the central nervous system (CNS). The BBB also interacts with perivascular macrophages (MΦs) and microglia, which play crucial roles in modulating the activation state of BBB components and themselves. Alterations in systemic metabolic and inflammatory states can lead to endothelial dysfunction, reducing BBB integrity and potentially allowing peripheral blood factors to leak into the CNS, triggering neuroinflammation. This review explores the intricate relationship between microglia and the BBB in health and disease, highlighting the importance of understanding these interactions for developing novel therapeutic strategies for neurological conditions involving immune and vascular mechanisms. Key topics include the functional roles of microglia, their interactions with the BBB, and their involvement in conditions such as stroke, diabetes, and systemic inflammation.