Exhaled breath contains relevant information on a person’s health status. Our vision is to use real-time and completely non-invasivechemical analysis of exhaled breath for applications such as medical diagnosis, monitoring progress and treatment of diseases, drug compliance, pharmacokinetics, and others. The methodology we use to analyze breath in real time is based on secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). It affords ppb-ppt limits of detection, and analysis of even semi-volatile compounds with molecular weights up to 1000 Da. Using complementary UHPLC-HRMS and MS/MS measurements of exhaled breath condensate and reference standards, it is possible to identify compounds in these “breathprints”. A number of interesting questions can now be addressed via on-line mass spectrometric analysis of exhaled breath: is there a core pattern for individual phenotypes visible in mass spectrometric “breathprints”? Can diurnal changes be monitored via exhaled breath? Can diseases be diagnosed via exhaled breath, and if yes, which ones? Can proper drug use (or drug abuse) be detected via analysis of the chemical composition of exhaled breath? This presentation will focus on several examples in medical diagnosis, including the detection of novel biomarkers for diseases such as obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Monitoring of drug compliance and pharmacokinetics via real-time SESI-MS will also be shown.