The regulation of ripening in fleshy fruits directly affects the quality and shelf life of such fruit, and extensive research has aimed to understand this regulation based on its agronomic importance. The identification of the key regulatory gene RIN in tomato has opened new horizons in our understanding of fruit ripening. RIN encodes a MADS-box transcription factor that functions as one of the earliest acting factors in the induction of ripening, and the molecular characterization of RIN has helped to elucidate the regulation of fruit ripening. Here I will review current advances in our understanding of the mechanisms that regulate fruit ripening in tomato, including the roles of RIN and other MADS-box proteins, mainly based on our recent studies. First, examination of the molecular properties of the RIN protein revealed that RIN has activities similar to SEPALLATA type MADS-box proteins. Next, identification of the direct transcriptional targets of RIN, via chromatin immunoprecipitation assays, demonstrated that RIN directly regulates a broad range of ripening-associated genes. Finally, identification of MADS-box proteins that interact with RIN revealed the functions of these proteins in ripening regulation. These studies clearly demonstrate the essential roles of MADS-box proteins in the regulation of tomato fruit ripening.