Human enteroviruses (HEVs) cause a wide range of diseases from upper respiratory tract infections to febrile rashes to the more serious neurological diseases of meningitis, encephalitis and acute flaccid paralysis. Understanding the phylogeny of HEVs is important as these diseases can spread rapidly causing outbreaks affecting large numbers of children, as exemplified by the spread of hand, foot and mouth disease due to enterovirus 71 through Asia. Accurate phylogenetic methods will improve diagnostics and potentially lead to new therapies for HEVs. Originally HEVs were classified based on serotyping but this was soon found to be insufficient due to the lack of antisera for the new HEV types. With the introduction of molecular phylogenetic typing, mainly based on sequencing of specific genes in the HEV genome, new classifications emerged, however, the relationship between the HEV genes is fluid due to the diversity and plasticity of the HEV genomes, such that the classification can vary depending on which gene is sequenced. Examining the whole genome has demonstrated that the gene order can change and that recombination is frequent, resulting in a complex mosaic of sequences derived from multiple parent HEVs. The degree of gene conservation, based on nucleotide substitution, also varies between the different genes. Therefore HEV typing is challenging and novel approaches are required when examining the whole genome of HEVs to fully understand the relatedness between HEV isolates. For HEVs, gene sequencing is not enough.