As a preamble, some historical and biographical brushtrokes of the Gioconda, Leonardo and his painting will be outlined. Following these observations, a series of medical interpretations will be put forth regarding his painting with the aim of analysing possible pathologies related to: the skin, hair, eyes, hands and the reproductive and endocrine systems. We will conclude by observing the famous work The Smile and by extracting a hypothesis on pathologies of various natures such as: neurological, muscular, hypoacusic, asthmatic, psychoneurotic, psychiatric, ethylic, sexual, stress-related, stomatological (bruxismo) and the driving force that lies behind setting off the Stendhal Syndrome: a psychosomatic disorder known to be due to the human being's susceptibility to saturation from having received impressions of great artistic beauty.