Healthcare practitioners, patient safety leaders, educators, and researchers increasingly recognize the value of human factors/ergonomics and make use of the discipline’s person-centered models of sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, “SEIPS 2.0.” SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement, and adaptation. The concept of configuration highlights the dynamic, hierarchical, and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at “a moment in time.” Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers, and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed.