Recent research has elucidated several different mechanisms for acupuncture. However, the interrelationship between these mechanisms and how acupuncture affects complex physiological systems is still not understood. Heart rate Variability (HRV), the beat-to-beat fluctuations in the rhythm of the heart, results from the regulation of the heart by the autonomic nervous system (ANS). Low HRV is associated with increased risk of all-cause mortality and is a marker for a wide range of diseases. Coherent HRV patterns are associated with increased synchronization between the two branches of the ANS, and when sustained for long periods of time result in increased synchronization and entrainment between multiple body systems. There is strong evidence from randomized placebo controlled trials that acupuncture modulates HRV. This may represent a mechanistic pathway for global physiological regulation, which is congruent with East Asian medical theory. The ability of acupuncture to improve HRV could be used as a tool in acupuncture research and practice to monitor treatment effectiveness and the impact on quality of life.