An HFE approach to system safety is presented, beginning with definitions of risk and hazard. The approach of Leveson is described using examples of real accidents and incidents. A detailed discussion of heuristic principles in decision making and how accidents can occur when people fall into “heuristic traps” is presented. The role of human error is discussed in detail and also a critical appraisal of the concept of “situation awareness” and its limitations as an explanatory principle. Risk homeostasis theory (RHT) is discussed and proposed as a model of the psychology of violations. Safety Culture and Safety Culture Maturity are also discussed and items for the design of a safety culture questionnaire are provided. Some examples of how interface design can either promote or prevent error are given, using a study of automated teller machines as an example. The chapter ends with an emphasis on the importance of taking a systems approach to safety and looking backward and outward from the event to the factors that led to the circumstances in place at the time the accident took place. This approach provides a richer insight into the causal networks that led to the accident and enables safety recommendations to be made at different levels and be directed to a wider range of authorities. Worked examples are given on the calculation of conjunctive and disjunctive probabilities, Bayes’ theorem, and the conduct of Hazard Identification Exercises (HAZID).