We propose a system for continuing surveillance of viral pathogens circulating in large human populations. We base this system on the physical isolation of viruses from large pooled samples of human serum and plasma (e.g., discarded specimens from diagnostic laboratories), followed by shotgun sequencing of the resulting genomes. The technology for concentrating virions from 100-L volumes was developed previously at Oak Ridge National Laboratory, and the means for purifying and concentrating virions from volumes in microliters have been developed recently. At the same time, marine virologists have developed efficient methods for concentrating, amplifying, and sequencing complex viral mixtures obtained from the ocean. Given this existing technology base, we believe an integrated, automated, and contained system for surveillance of the human "virome" can be implemented within 1 to 2 years. Such a system could monitor the levels of known viruses in human populations, rapidly detect outbreaks, and systematically discover novel or variant human viruses.