Self-rated health (SRH)—a person’s subjective evaluation of his general health—is a more valid and powerful predictor of morbidity and mortality than any other combination of objective and self-reported measures. However, current theoretical frameworks fail to explain this association. Here, we sought to investigate SRH in relation to health outcomes from a transdisciplinary perspective. Using a selective review of epidemiological, clinical and qualitative SRH literature, we analyzed the relationships between this global subjective self-perception of health (the whole) and its directly measurable constituents (the parts). Although SRH often predicts major health outcomes, its underpinnings vary from person to person. Factors influencing individual’s health interact in complex ways evade reductionist methods assessing the parts, and may be best captured by global self-perceptions of health. The study of SRH from a transdisciplinary perspective exemplifies the notion that the whole is greater than the sum of its parts. Insight into individual’s experience of “health”, their association with physiological processes, and impact on the health/disease continuum may contribute to the development of individualized strategies for health care and promotion with aging. In particular, this should be most valuable for addressing non-communicable health conditions where cross-talk between health domains (biological, psychological, social, behavioral, spiritual) may significantly contribute to pathophysiology.