This paper describes an innovative method, and related equipment, developed by the authors to monitor non-invasively historic panel paintings under museum display conditions. This method permits in-depth knowledge about such artworks, allowing us to understand their reactions to climatic variations, and pro- vides objective data on which conservation decisions can be confidently based, since the data are directly obtained from the individual artwork. Since 2004, following the invitation from the Louvre Museum and the C2RMF (National Centre for Research and Restoration of French Museums), the wooden panel on which Leonardo da Vinci painted his Mona Lisa has been studied by an international research team of wood technologists and engineers, including researchers from French and Italian universities and related scientific institutions (Montpellier, Clermont Auvergne, Poitiers, Florence), to understand its mechanical, hygroscopic and shape characteristics and behaviour, to evaluate its present state, and to provide sug- gestions for optimizing its conservation conditions. Non-invasive methods and equipment were therefore devised and implemented to measure (during the annual opening day of its display case) and automat- ically monitor (during the time the display case remains closed) both the deformations that the panel undergoes (mainly produced by the inevitable small climatic fluctuations within the case) and the con- straining forces acting on the panel itself. The method and the related equipment, improved over the years, are based on miniature load cells and displacement transducers, whose outputs are automatically logged at desired time intervals, typically ranging between 30 min for monitoring during the whole year, and a few seconds for manual measurements, calibrations, and other selected events; the stored data can be downloaded both through a cable connection and wirelessly, by means of a specially developed con- nection apparatus. The panel is confined in a climate-controlled display case, which typically is opened only for a few hours once a year. Additionally, close restrictions must be respected, including absolute non-invasiveness, non-interference with the enjoyment of the artwork by the public, and compliance with strict procedures for safe and secure conservation. The implementation of this method has provided significant information about the actual behaviour of the panel during the whole year. Comparing several annual force-deformation curves, their good linearity suggests that no unacceptable stress or deformation has taken place in it, showing that the climatic conditions (air temperature and relative humidity) main- tained in the display case can be considered favourable to the conservation of the artwork. Moreover, based on the collected data, reliable Finite Element Method (FEM) models are being developed and cali- brated, with the aim of describing the mechanical behaviour of the panel and virtually evaluating the risk of damage (including the propagation of an ancient crack) deriving from external conditions or actions to which it would be unthinkable to submit the original historic artwork.