OBJECTIVE: The aim of the study was to address the need for explicit recognition that obesity is complex in its biological, social, psychological, and societal determinants and ramifications, and that applications of programs to address obesity at the workplace need to recognize this setting as a complex social environment. Efforts to address this complexity more meaningfully demand intentional application of systems science principles and approaches. METHOD: Along with several relevant examples, a description of systems sciences and the application of its principles to obesity and the workplace setting are presented. CONCLUSIONS: Systems science provides a method to explore large proportions of unexplored potential and unexplained variation in obesity research as applied to the workplace.