Although the association remains controversial, enteroviruses have been implicated in the aetiology of several chronic diseases in humans. Investigations in vitro lead to better understanding of virus-cell interactions, and improve our knowledge of the molecular factors that are involved in the establishment and maintenance of these infections. Recent findings suggest that the most important factor in the establishment of a persistent infection is receptor usage. Studies of the mechanisms that are at work in these in-vitro models of viral infection have shown that there is frequently a co-evolution of mutant cells with higher resistance to viral infection and of virus variants with increased virulence (i.e. variants with the ability to utilize other cell-surface molecules as receptors).