The association of self-rated health with mortality is well established but poorly understood. This paper provides new insights into self-rated health that help integrate information from different disciplines, both social and biological, into one unified conceptual framework. It proposes, first, a model describing the health assessment process to show how self-rated health can reflect the states of the human body and mind. Here, an analytic distinction is made between the different types of information on which people base their health assessments and the contextual frameworks in which this information is evaluated and summarized. The model helps us understand why self-ratings of health may be modified by age or culture, but still be a valid measure of health status. Second, based on the proposed model, the paper examines the association of self-rated health with mortality. The key question is, what do people know and how do they know what they know that makes self-rated health such an inclusive and universal predictor of the most absolute biological event, death. The focus is on the social and biological pathways that mediate information from the human organism to individual consciousness, thus incorporating that information into self-ratings of health. A unique source of information is provided by the bodily sensations that are directly available only to the individual him- or herself. According to recent findings in human biology, these sensations may reflect important physiological dysregulations, such as inflammatory processes. Third, the paper discusses the advantages and limitations of self-rated health as a measure of health in research and clinical practice. Future research should investigate both the logics that govern people's reasoning about their health and the physiological processes that underlie bodily feelings and sensations. Self-rated health lies at the cross-roads of culture and biology, therefore a collaborative effort between different disciplines can only improve our understanding of this key measure of health status.