The role of inherently safer design (ISD) in process safety assurance has changed significantly over the past 40 years. When first introduced by Professor Trevor Kletz following the 1974 Flixborough explosion, the ISD concept challenged the manner in which process risk was addressed in the chemical industry. The prevailing view of adding on safety devices and implementing procedures aimed at controlling hazards was now complemented by a way of thinking that sought to remove or reduce hazards at their source. The past 20 years have seen ISD mature into an established risk reduction strategy that is widely known in principle and increasingly adopted in practice. The current paper reviews the authors' collaborative research efforts aimed at integrating ISD into various process safety systems, activities, and applications. The primary inherent safety principles (minimization, substitution, moderation, and simplification) are explained with example‐based guidance provided for their use. ISD features and performance indices are examined throughout the early design and operational stages of a typical process life cycle. Preventing and mitigating undesirable occurrences such as domino effects and dust explosions are shown to be feasible by adopting an inherent safety approach. The importance of reviewing ISD case studies developed from incident investigations is also discussed. Finally, we present our personal opinions on the current status of inherently safer design and future possibilities for its continued growth.