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Abstract: The illness and death of Isabella Medici Orsini     Isabella de'Medici, the daughter of the granduke of Tuscany Cosimo I, died in Cerreto Guidi’s villa on 16 july 1576. The shocking succession of deaths in the family of Cosimo I, some decidedly suspect, fueled the spread of legendary interpretations within the anti Medici faction. According to tradition, Isabella was strangled to death by her husband, Paolo Giordano Orsini, first duke of Bracciano. The inflexible accusatory theory has it that her murder was was agreed upon by her husband and brothers to put an end to an adulterous relationship that risked damaging the family honour. In spite of a total lack of evidence or of reliable sources, later historiography has always taken the crime for granted without ever considering the possibility of a natural death. A study of the corrispondence between Paolo Giordano Orsini and Isabella de’Medici preserved in Orsini family archive in the Archivio Storico Capitolino, not only contradicts the traditional hypothesis, but provides evidence of the long illness that led to Isabella’s death. This essay describes the progress of her illness, the doctors’ treatments and the behaviour of those close to her.