Policy makers and researchers are increasingly recognizing the connections between public health and transportation, but health improvements are typically framed from a physical health perspective rather than considering broader quality of life (QOL) impacts. Currently, there is a limited understanding of the ways in which transportation and QOL intersect, and little is known about how metropolitan planning organizations (MPOs) in the United States are addressing QOL outcomes. This study addressed these gaps by developing a conceptual framework holistically linking transportation to QOL. The proposed framework identified four transportation-related QOL dimensions—physical, mental, social, and economic well-being—which are predominantly influenced by three components of the transportation system: mobility/accessibility, the built environment, and vehicle traffic. This framework then formed the basis for a content analysis of 148 long-range transportation plans in the United States to evaluate the extent to which QOL is being considered in the planning process. The results of the analysis and a follow-up examination of 13 plans revealed that MPOs are inconsistently addressing QOL. Plans primarily targeted QOL enhancement from the perspective of physical well-being, while mental and social well-being were rarely considered. Policy recommendations were provided to more comprehensively integrate QOL into the transportation planning process.