The clinical presentation of systemic vasculitis can vary widely and include skin disorders, neuropathy, eye symptoms, and systemic inflammation. The precise molecular mechanisms underlying this syndrome are not fully understood, but the importance of a chronic imbalance of the cytokines and chemokines involved in orchestrating inflammatory responses is now recognized. In similar fashion, atherosclerosis is now recognized to be a chronic inflammatory disease in which chemokines play important roles. In the current review, we discuss the involvement of CX3CL1, which is a unique member of the chemokine family, and its receptor, CX3CR1, in the pathogenesis of these vasculopathies.