A major public health challenge today is the problem of congenital cytomegalovirus (CMV) transmission. Maternal-fetal CMV infections are common, occurring in 0.5-2% of pregnancies, and these infections often lead to long-term injury of the newborn infant. In spite of the well-recognized burden that these infections place on society, there are as yet no clearly established interventions available to prevent transmission of CMV. In order to study potential interventions, such as vaccines or antiviral therapies, an animal model of congenital CMV transmission is required. The best small animal model of CMV transmission is the guinea pig cytomegalovirus (GPCMV) model. This article summarizes the GPCMV model, putting it into the larger context of how studies in this system have relevance to human health. An emphasis is placed on how the vertical transmission of GPCMV recapitulates the pathogenesis of congenital CMV in infants, making this a uniquely well-suited model for the study of potential CMV vaccines.