The RNA of all members of the Picornaviridae family initiates translation internally, via an internal ribosome entry site (IRES) element present in their 5' untranslated region. IRES elements consist of cis-acting RNA structures that often operate in association with specific RNA-binding proteins to recruit the translational machinery. This specialized mechanism of translation initiation is shared with other viral RNAs, and represents an alternative to the general cap-dependent initiation mechanism. In this review we discuss recent evidences concerning the relationship between RNA structure and IRES function in the genome of picornaviruses. The biological implications of conserved RNA structural elements for the mechanism of internal translation initiation driven by representative members of enterovirus and rhinovirus (type I IRES) and cardiovirus and aphthovirus (type II IRES) will be discussed.