Susceptibility to type 1 diabetes (T1D) is dictated by a complex interplay between genetic determinants and environmental influences. Accumulating evidence strongly supports viral infection as an important factor in the etiology of T1D. To this effect, several viruses have been associated with the capacity to induce or exacerbate T1D in both humans and mice. The most convincing evidence linking viral infection and autoimmunity comes from studies on enteroviruses, particularly coxsackievirus. In this review we will discuss the evidence associating coxsackievirus infection to T1D and present the current state of knowledge on the potential mechanism of coxsackievirus-mediated T1D.