Acceptance and commitment therapy (ACT) is one of the most popular “third wave” therapies. In scores of head-to-head studies with cognitive behavioral therapy (CBT), research shows ACT to be either comparable or superior. This chapter describes the core principles of ACT in relationship to current neuroscience formulations and known mechanisms impacted by heart rate variability biofeedback (HRVB). Combining HRVB with ACT offers advantages for a variety of physical, stress-related, and psychological disorders. The author concludes that ACT is a better fit with HRVB than CBT or other therapeutic approaches. A case example illustrates the integration of ACT and HRVB.