The overall goal of the Congenital and Perinatal Infections Consortium (CPIC) is to establish infrastructure and institutional cooperation – focusing on rare congenital and perinatal viral infections – to advance understanding of these diseases, improve clinical trial readiness, test therapies, advance patient care, and ultimately reduce disease burden. These infections include congenital cytomegalovirus (CMV) disease, neonatal herpes simplex virus (HSV) infection, and neonatal viral sepsis caused by enteroviruses (EVs) and the related human parechoviruses (HPeVs). Led by researchers at the University of Alabama at Birmingham (UAB) and supported by an experienced and highly efficient study team, the 28 study sites that will comprise the CPIC have cooperated closely for decades as the Collaborative Antiviral Study Group (CASG) to investigate the natural history and treatment of rare congenital and perinatal infectious diseases. These longstanding relationships, as well as partnerships with community and industry stakeholders, will facilitate the success of our research efforts and our mentored career enhancement activities. As with all successful research programs, answers to critical questions always lead to identification of the next important questions that will further advance the field. These questions are the basis of the CPIC research portfolio that will advance the care of children with rare neonatal viral infections and provide experiential mentored research opportunities as we train the future generation of rare diseases researchers. Aims of the CPIC are: 1) to build upon clinical research advances achieved by the CASG to further advance the diagnosis, treatment, and understanding of HSV, CMV, and EV in the neonatal population; 2) to leverage longstanding relationships across the 28 CPIC study sites and with stakeholders to conduct clinical research projects with the highest of fidelity to all research standards; 3) to advance rare diseases research by sharing standardized data through close partnership with the Data Management and Coordinating Center and by utilizing cloud computing capacities and Common Data Elements; 4) to develop and utilize pilot and feasibility funding to leverage existing institutional resources and maximize its impact on the advancement of the science related to rare infectious diseases impacting neonates; and 5) to support mentored research and career enhancement opportunities for clinical fellows and junior faculty to facilitate the development of early-stage investigators in rare diseases research. Our Consortium will bring value to the Rare Diseases Clinical Research Network by promoting unique understanding of these diseases, and by providing both a time-tested research model and advanced pharmacometric expertise.