Seed dispersion and consequent plant propagation depend on the success of fruit ripening. Thus, ripening is a highly regulated developmental process aiming to maximize fruit organoleptic traits to attract herbivores. During ripening, the developing fruit experiences dramatic modifications, including color change, flavor improvement, and loss of firmness that are remarkably coordinated. Dynamic interactions between multiple hormones, transcription factors, and epigenetic modifications establish the complex regulatory network that controls the expression levels of ripening-related genes. Tomato, as a climacteric fruit, displays a burst of respiration once the seeds mature, followed by an increase in ethylene that regulates ripening. The accepted paradigm of the ripening transcriptional regulation has been recently challenged by the generation of true-null mutants of the previously considered master regulators of ripening. In addition to hormonal and transcriptional control, epigenetic shifts regulate the ripening process. Future research will contribute to better understanding the factors regulating fruit ripening.