This paper provides a theoretical perspective on human factors and ergonomics (HFE), defined as a unique and independent discipline that focuses on the nature of human-artefact interactions, viewed from the unified perspective of the science, engineering, design, technology and management of human-compatible systems. Such systems include a variety of natural and artificial products, processes and living environments. The distinguishing features of the contemporary HFE discipline and profession are discussed and a concept of ergonomics literacy is proposed. An axiomatic approach to ergonomics design and a universal measure of system-human incompatibility are also introduced. It is concluded that the main focus of the HFE discipline in the 21st century will be the design and management of systems that satisfy human compatibility requirements.