The upgrade of PTR-MS from Quadrupole to Time of Flight mass spectrometer [1] represents a great advance in the analytical capability of PTR-MS technology. Due to higher mass range and higher mass and time resolution [2-3], ToF mass analyzers appears to be an ideal tool for breath monitoring. On the other hand the larger and more complex data generated requires great efforts to handle and extract the analytical information. We recently developed a full methodology from basic mass spectra handling to the application of up-to date data mining methods [4] which allows for extracting highly relevant features from large amounts of complex spectral data. Here we present our recent experiences in breath monitoring using PTR-ToF-MS for non-invasive physiology monitoring and disease diagnosis. The first application is the monitoring of the effects of the diet on the physiology state in awake rats affected by non-alcoholic steatohepatitis (NASH)[5]. The second application is the implementation of a procedure for the diagnosis of liver cirrhosis and the assessment of disease severity in humans