Enteroviruses (EVs) are small nonenveloped RNA viruses. The genus Enterovirus makes up the Picornaviridae family together with the genera Aphthovirus, Avihepatovirus, Cardiovirus, Erbovirus, Hepatovirus, Kobuvirus, Parechovirus, Sapelovirus, Senecavirus, Teschovirus and Tremovirus. Picornaviruses are classified in the order Picornavirales. The Enterovirus genus currently consists of ten species [301], which are further divided into multiple serotypes. An EV species is defined as a polythetic class of phylogenetically related serotypes or strains that share a limited range of natural hosts and host cell receptors, a significant degree of compatibility in proteolytic processing, replication, encapsidation and genetic recombination, greater than 70% amino acid identity in P1, 2C and 3CD proteins (for all EV genome map see Figure 1A and below) and have a genome (G+C) base composition that varies by no more than 2.5% [1]. Seven of the species; human EV (HEV)-A, HEV-B, HEV-C, HEV-D, human rhinovirus A (HRV-A), HRV-B and HRV-C, are known to infect humans ( Figure 1B). The other species of the genus infect monkeys (Simian EV-A and an as yet unclassified novel species consisting of types SV-6, EV-103 and EV-108 isolated from captive simians [2,3]), bovines (bovine EV) and pigs (porcine EV-B).The EV genome is a single-stranded positivesense RNA molecule of approximately 7500 nucleotides, consisting of a single open reading frame flanked by 5´ and 3´ noncoding regions (NCRs) [4]. The 5´ NCR contains two functional domains; a cloverleaf, which is a cis-acting element in viral replication [5,6] and an internal ribosome-binding site, which is essential for translation initiation [7][8][9]. The 3´ NCR forms highly conserved secondary and tertiary structures that are important in replication initiation [10][11][12][13]. The open reading frame is translated into a single, large polypeptide, which is subsequently cleaved by viral proteases (reviewed in [14]). The polypeptide is divided into three domains, P1-3, consisting of three to four proteins each. The P1 region contains viral capsid proteins VP1-4, whilst P2 and P3 contain the nonstructural proteins 2A-C and 3A-D, respectively ( Figure 1A).Several new EV serotypes and a new HRV species have been characterized in the Enterovirus genus recently. In this article we will focus on the evolution and emergence of new EVs. By definition a new EV type means a previously unknown capsid type, since recombination at the 5´NCR and nonstructural protein coding region appears to be a prominent feature for both new and previously known EV serotypes (see below, [15][16][17][18][19]). In this article we use the term new or newly described virus for those HEV and HRV types that have been characterized by molecular methods (sequence comparison) rather than by antigenical typing methods ('classic' HEV and HRV serotypes). Since at least most of the recently characterized new EVs are not newly arisen but rather newly detected (see below), the question about the origin of the new EV types can ...