A new Psycho-Social System Approach to Well-Being is presented, in which psychological and social functioning is understood through an empirically derived framework of five domains. A quantitative co-term analysis was performed on 3466 terms within 18,401 PsycINFO® journal documents on topics related to positive psychology (PP) across disciplines such as psychology, education, management, business, and psychiatry. The analysis revealed that research on PP topics has concerned five broad domains: attention and awareness, comprehension and coping, emotions, goals and habits, and virtues and relationships. These domains provide a new systematic framework, the Five Domains of Positive Functioning, for understanding positive psycho-social functioning and exploring the underlying ways in which people function to achieve well-being outcomes. When used within the Psycho-Social System Approach, the new framework can be used in future research to clarify mechanisms of change, facilitate comparisons between different PP interventions, and suggest ways to improve intervention effectiveness.