In order to decrease costs and increase competitiveness, nuclear utilities use more challenging operational conditions, longer fuel cycles and higher burnups, which require modifications in fuel designs and materials. Different aspects of quality assurance and control, as well as analysis of fuel performance have been considered in a number of specialized publications. The present publication provides a concise but comprehensive overview of all interconnected quality and reliability issues in fuel fabrication, design and operation. It jointly tackles technical, safety and organizational aspects, and contains examples of state of the art developments and good practices of coordinated work of fuel designers, vendors and reactor operators.