The remains of 12 members of the grand ducal (junior) branch of the Florentine Medici family were exhumed in 2003 as part of the Medici Project, a multidisciplinary study whose aim was to investigate the lifestyles, health status, and possible causes of death of members of one of the richest, most powerful families of the Italian Renaissance. Digital radiography and orthopantomography were performed on the skeletal remains of individuals who lived between 1562 and 1666. The observed bone malformations, deformities, and changes (degenerative, metabolic, and dental) challenge traditional views, based on portraits and historical accounts, about the appearance and lifestyle of some family members. Moreover, the occurrence of a constellation of bone changes related to diabetes (osteoporosis, osteoarthritis, diffuse idiopathic skeletal hyperostosis, cranial hyperostosis, and crystalline arthropathy) suggests that this metabolic disease was common in the grand ducal branch of the Medici family.