Psychoneuroimmunology is a framework for mind–body practice and research that combines cutting-edge scientific exploration with holistic philosophy to appreciate and understand stress responses. The rapidly growing research literature provides a foundation for building an integrative stress management model with the potential to positively influence the stress–disease relationship and, ultimately, health outcomes. This article introduces a novel tai chi intervention and provides quantitative and qualitative data from a randomized clinical trial indicating its effects on psychosocial variables in individuals living with various stages of HIV disease.