The shift towards non-communicable, chronic, diseases has placed emphasis on understanding the dominant role our everyday activities and broader environment as a major determinant of health. The realization that genetics is but one of the drivers of maintaining health and developing chronic diseases, necessitates that we refocus our attention on the patient and the interactions between life style and environment and the biology and physiology underlying health and chronic diseases. In that respect, we begin to better appreciate that health and disease are fundamentally systems properties and need to be treated as such. In this review, we attempt to first, define the "patient" eco-system, its boundaries and its components and then discuss how to establish and assess the multitude of interactions across the system components. We particularly focus on three environmental and life-style factors: mistimed rest/activity patterns, mistimed feeding patterns and chronic stress. (C) 2019 Elsevier Ltd. All rights reserved.