From birth, social relationships have emotional and self-regulating properties that operate through different body systems. This chapter explores how heart rate variability (HRV), an index of the parasympathetic regulation of the heart (via the vagus nerve), is a central element of the physiological underpinnings of sociality and mental health, with important implications for the clinical practice of compassion focused therapy. HRV is associated with the experience of inter- and intrapersonal safeness, and the inhibitory function of the prefrontal cortex linked to prosocial motives, such as compassion. However, a modern neurovisceral integration perspective suggests that HRV is also a biomarker of the functioning of a set of neural structures through which the brain regulates visceromotor, neuroendocrine, and behavioural responses that are critical for psychophysiological adaptability. This chapter reviews the main body-based practices (including breathing, yoga, nutrition, and supplements) that can be used in compassion-focused interventions to facilitate the emergence of safeness and, via increased vagal regulation, promote clinical change.