The incremented sensitivity and availability of NAATs for detection of virtually any clinically germane virus have revolutionized testing in the clinical virology laboratory. In many laboratories, NAATs have supplanted virus culture, antigen detection methods, and direct molecular hybridization techniques. Three approaches have been taken: target amplification such as PCR, strand displacement amplification, nucleic acid sequence & amplification, and transcription-mediated amplification systems; probe amplification, including replicase and ligase chain reaction; and signal amplification, such as branched-chain DNA assay and hybrid capture assay. Several commercial and in-house assays have been developed. Quantification of viral genome in plasma or serum can be acclimated to determine prognosis, cull patients for antiviral therapy, and monitor replication to treatment in a variety of patient populations. Multiplex assays capable of detecting several viruses in a single amplification reaction have been developed and studies suggest that these assays are cost-efficacious. The development of automated genuine-time PCR utilizing fluorescence techniques and perpetual detection of amplified product has abbreviated detection times substantially relative to conventional PCR assays. Because these assays utilize a closed system they withal are less prone to contamination than conventional PCR. NAAT has been applied to genotyping of viruses as well as for the detection of mutations that confer resistance to antiviral agents. More incipient molecular techniques such as pyrosequencing and whole-genome sequencing are commencing to be applied in the clinical laboratory and are providing ameliorated genotyping of viruses, detection of virus quasispecies, and metagenomic analysis for detecting subsisting and incipient or novel viruses in clinical specimens.