We propose a transdisciplinary, life span framework for examining the underlying cause of the observed intergenerational decline in health among Hispanic Americans. We focus on acculturation, and we posit that acculturation-related processes in first-generation Hispanic immigrant mothers may affect the intrauterine development of an unborn child, via the process of fetal programming, to produce phenotypic effects that may alter the susceptibility for noncommunicable chronic diseases. In this manner, an intergenerational cascade of perpetuation may become established. Our framework may shed light on the biological, behavioral, and social causes of intergenerational cycles of vulnerability among immigrant minority groups, with public health and policy implications for primary prevention and intervention.