Atherosclerosis is a chronic inflammatory disease of the arterial wall, and T-cell-mediated immune responses to plaque antigens are a prominent component of the inflammatory process. In addition to antigen stimulation, T-cell responses require co-stimulatory signals, the best defined of which are delivered by B7 family molecules on antigen-presenting cells binding to CD28 on T cells. T-cell co-stimulation directly influences the CD40/CD154 immunoregulatory pathway, which is well known to influence atherosclerosis. This review discusses recent progress in understanding the role of B7 family molecules in atherosclerosis, and T-cell co-stimulation as an important link between innate immunity and adaptive immune responses to plaque antigens.