**Abstract**

While the important role of the autonomic nervous system (ANS) has been historically underappreciated, recently there has been a rapid proliferation of empirical, methodological and theoretical progress in our more detailed understanding of the ANS. Previous more simplistic models of the role of the ANS using the construct of homeostasis have been enhanced by the use of the construct of allostasis and a wide variety of technological innovations including wearable and implantable biosensors have led to improved understanding of both basic and applied knowledge. This chapter will explore in particular heart rate variability (HRV) as a rich variable which has developed an extensive literature, beginning with predicting all-cause mortality, but now encompassing a wide variety of disease and illness states; cognitive, affective and behavioral processes and performance optimization. A critical analysis of HRV from the perspective of complex adaptive systems and non-linear processes will be included and innovative future uses of HRV will be described.

**Keywords:** ANS, HRV, Digital epidemiology, Smart health, regenerative and biomic medicine
