One of the reasons the 1997 Technical Advisory Group on Vaccine-Preventable Diseases recommended acceleration of rubella and congenital rubella syndrome (CRS) prevention efforts was the fact that the enhanced measles surveillance system in the Americas found that 25% of reported measles cases were laboratory-confirmed rubella cases. Until 1997, the laboratory network primarily focused on measles diagnosis. Since 1999, due to the accelerated rubella control and CRS prevention strategy, laboratories have supported the regional measles, rubella, and CRS elimination goals. The measles-rubella laboratory network established in the Americas provides timely confirmation or rejection of suspected measles and rubella cases, and determination of the genotypic characteristics of circulating virus strains, critical information for the programs. A quality assurance process has ensured high-quality performance of procedures in the network. Challenges are occurring, but the measles-rubella laboratory network continues to adapt as the requirements of the program change, demonstrating the high quality of the laboratories in support of public health activities and elimination goals.