Enteroviruses, members of the Picornaviridae family, are common viruses associated with clinical manifestations ranging from mild respiratory symptoms to serious conditions, including aseptic meningitis, encephalitis, neonatal sepsis, and acute flaccid paralysis. Approximately 100 serotypes of nonpolio enteroviruses have been recognized, and some viruses previously classified as enteroviruses, namely echovirus 22 and 23, recently have been reclassified as human parechoviruses (HPeVs), a different genus within the Picornaviridae family. This report describes trends in nonpolio enterovirus and HPeV detections during 2006-2008, based on data from two laboratory-based surveillance systems, the National Enterovirus Surveillance System (NESS) and, for the first time, the National Respiratory and Enteric Virus Surveillance System (NREVSS). As in previous years, approximately 70% of detections occurred during July-October, the peak enterovirus season. The five most common enterovirus serotypes (coxsackievirus B1 [CVB1], echovirus 6, echovirus 9, echovirus 18, and coxsackievirus A9) accounted for 54% of total serotyped detections. During 2006-2008, southern states reported the most serotyped enterovirus detections, followed by midwestern states, western states, and the northeastern states. In 2007 and 2008, CVB1 was the predominant serotype detected, accounting for 24% and 19% of overall detections, respectively. In 2007, CVB1 was implicated in an outbreak of serious neonatal infections in the United States. Understanding trends in enterovirus and HPeV circulation can help clinicians decide when to test for these infections. Also, more timely reporting of data could help public health officials recognize outbreaks associated with these viruses.