Human parechoviruses (HPeVs) are members of the large and growing family of Picornaviridae. Although originally described as echovirus 22 and 23 within human enteroviruses because of their clinical and morphological properties, they have since been shown to be distinct from this and other picornavirus groups in several features of their genome organisation, structure and replication. Human parechoviruses show genetic and antigenic heterogeneity and a number of distinct HPeV types are known to circulate widely in human populations throughout the world. Although the majority of HPeV infections occur early in life without specific symptoms, disease manifestations associated with many of the currently described types have been described, ranging from gastroenteritis and respiratory infections to neurological disease, particularly in neonates. Although HPeV diagnosis has historically been made by virus isolation, a new generation of sensitive and specific molecular tests for HPeV RNA promises to greatly improve the effectiveness of HPeV detection and type identification, as well as providing a greater understanding its molecular epidemiology. By this means, we will learn much more about the clinical relevance of HPeVs and the association of different HPeV types with specific disease presentations.