Among the profoundly signi cant messages of Man’s Search for Meaning (Frankl, 1946/1992) was the observation that those individuals who maintained a sense that life had meaning and purpose, even amid the horrors of a Nazi concentration camp, survived longer. As a physician, Frankl re ected on this idea in terms of the workings of the body’s biological systems and, in particular, immune processes. In this chapter, scienti c evidence suggesting that possessing a strong existential well-being is, in fact, accompanied by (and possibly promotes) better biological regulation and better health is examined. is agenda, for which emerging empirical ndings are preliminary and partial at best, converges with e orts to foster a perspective on “positive health” that is fundamentally concerned with explicating the physiological substrates of human ourishing (Ry & Singer, 1998). us, rather than de ne human health as the absence of illness, the positive-health approach begins with the presence of wellness and then probes the neural circuitry and biological processes that underlie it. Probing the inner workings between well-being, the brain, and biology is the essential quest for understanding positive health.