The coxsackievirus and adenovirus receptor (CAR) has been studied extensively since its identification and isolation in 1997. The CAR is an immunoglobulin superfamily protein with two extracellular Ig-like domains, a single membrane-spanning sequence, and a significant cytoplasmic domain. It is structurally and functionally similar to the junctional adhesion molecules. The amino terminal domain, distal from the membrane, has been structurally characterized alone, bound to the adenovirus fiber knob, and, in full-length CAR, docked in the canyon structure of the coxsackievirus capsid. Although the past decade has produced a burst of new knowledge about CAR, significant questions concerning its function in normal physiology and coxsackievirus-related pathology remain unanswered.