Long-standing neck pain (LNP) is a clinical condition frequently encountered in the physical therapy clinic. LNP is a complex, multifactorial condition affecting multiple body systems including the autonomic nervous system (ANS). Traditionally, research on the impact of physical therapy on LNP has focused on self-report measures and pain scales. Heart rate variability (HRV) is an objective measure of the ANS, allowing for quantification of effects of treatment. This systematic review is intended to evaluate if manual therapy acutely affects heart rate variability in adults with long-standing neck pain.