This paper discusses general principles, assumptions and challenges in management of fatigue in operating NPP’s. The roots and state-of-the-art in different design codes, design curves and rules are briefly reviewed. It is noted that the ASME Boiler and Pressure Vessel Code, Section III was originally prepared as a Design Code to ensure appropriate design and manufacture of nuclear vessels. ‘Design by Rule’ was replaced by ‘Design by Analysis’. Today, ASME III and the related international codes are also used for ‘Operation by Analysis’. Demonstration that the fatigue usage factor is less than unity is not sufficient for proactive component life management. Quantitative analyses of fatigue usage and factors affecting it are needed, including the environmental effects. Differences between the design curves and penalty factors for environmental effects are illustrated through selected examples.