Obesity is a serious and costly societal issue that, combined with other biobehavioral risk factors, contributes to chronic cardiometabolic illnesses. Stress reactivity is posited as a causal mechanism in the development of obesity and cardiometabolic diseases, with maladaptive outcomes associated with both high and low stress reactions. Emotion regulation ability (ERA) represents an entry point for individuals to alter their stress response, leading to reduced risk for illness. This program of research sought to understand the ways in which stress reactivity and ERA interact to influence behavioral and physical health. Study One explored the interaction between perceived stress reactivity and ERA in predicting obesity-related health outcomes. Results revealed that only those reporting higher perceived reactivity benefited from the ability to down-regulate negative emotions, as indicated by lower body mass index and Type 2 diabetes incidence. To further explore ERA in a health-context, Study Two developed a novel ERA task that assesses the up- and down-regulation of negative emotions toward obesity-related health stimuli. Study Three used this task to test whether health-focused ERA modulates the influence of perceived and physiological stress reactivity on biobehavioral health. Analyses revealed that perceived stress reactivity and ERA interacted to predict sleep quality and blood pressure. This program of research highlights the ways in which psychological, emotional, and biobehavioral health interactions can inform patient-centered and individualized approaches to medicine.