Human–Systems Integration (HSI) is holistic, considering a multi-agent world composed of humans and machines. Human-centeredness is related to operations and usages. human-centered design breaks with traditional technology-centered engineering that considers operations too late in systems development processes. Circa 1980s, a new discipline started to emerge in computer science, human–computer interaction. Intrinsic events may be caused by physical, physiological, or psychological processes constraining human performance. Extrinsic events may be caused by sociological, organizational, or environmental processes impacting human performance. Engineering-oriented human-centered disciplines have evolved toward HSI, together with the evolution of complexity science and artificial intelligence useful in engineering design. HSI departs from the traditional approach that considers engineering first and people second, leading to concepts of user interface and training, developed in sequence once an engineered system is almost developed. The chapter also presents an overview of the key concepts discussed in this book.