The microRNA family, miR-181, plays diverse roles in regulating key aspects of cellular growth, development, and activation. Accumulating evidence supports a central role for the miR-181 family in vascular inflammation by controlling critical signaling pathways, such as downstream NF-κB signaling, and targets relevant to endothelial cell activation and immune cell homeostasis. This review examines the current knowledge of the miR-181 family’s role in key cell types that critically control cardiovascular inflammation under pathological and physiological stimuli.