Fruit has evolved myriad forms that facilitate seed dispersal in varied environmental and ecological contexts. Because fleshy fruits become attractive and nutritious to seed-dispersing animals, the transition from unripe to ripe fruit represents a dramatic shift in survival strategy-from protecting unripe fruit against damaging animals to making it appealing to those same animals once ripened. For optimal fitness, ripening therefore must be tightly controlled and coordinated with seed development. Fruits, like many vegetative tissues of plants that contribute to human diets, are also subject to decay, which is enhanced as a consequence of the ripening transition. As such, ripening control has enormous relevance for both plant biology and food security. Here, we review the complex interactions of hormones and transcription factors during fleshy-fruit ripening, with an emphasis on the recent discovery that epigenome dynamics are a critical and early regulator of the cascade of molecular events that ultimately contribute to fruit maturation and ripening.