Parechoviruses belong to the large family of small RNA viruses called Picornaviridae (pico—small, RNA). Picornaviruses are clinically and economically important viruses characterized by a small icosahedral protein capsid structure that contains a single-stranded, positive-sense viral RNA genome (1). These viruses show great diversity in their host tropism, usage of viral proteins, exploitation of host lipid and protein functions at different steps of the viral life cycle, and disease manifestations in humans and other vertebrate and invertebrate hosts. The Parechovirus genus is one of the Picornaviridae family genera, which contains viruses within six parechovirus species, Parechovirus A-F, that infect multiple vertebrate species (Fig. 1). Recent parechovirus-associated pediatric disease outbreaks in different parts of the world (2–4) highlighted the importance of dedicated surveillance and a greater understanding of the biology and disease manifestations caused by these understudied viruses. In this review, we summarize the history of human and nonhuman parechovirus isolation, global seroprevalence and distribution, viral biology, and evolution, considering these factors might contribute to their host specificity, virulence, tissue tropism, pathogenesis, host immunity, and population dynamics.