Fruits are derived from flowers and play an important role in human food, nutrition, and health. In general, flowers determine the crop yield, and ripening affects the fruit quality. Although transcription factors (TFs) only account for a small part of plant transcriptomes, they control the global gene expression and regulation. The plant-specific NAC (NAM, ATAF, and CUC) TFs constitute a large family evolving concurrently with the transition of both aquatic-to-terrestrial plants and vegetative-to-reproductive growth. Thus, NACs play an important role in fruit yield and quality by determining shoot apical meristem (SAM) inflorescence and controlling ripening. The present review focuses on the various properties of NACs together with their function and regulation in flower formation and fruit ripening. Hitherto, we have a better understanding of the molecular mechanisms of NACs in ripening through abscisic acid (ABA) and ethylene (ETH), but how NACs regulate the expression of the inflorescence formation-related genes is largely unknown. In the future, we should focus on the analysis of NAC redundancy and identify the pivotal regulators of flowering and ripening. NACs are potentially vital manipulation targets for improving fruit quantity and quality.