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Abstract: The analysis of volatile organic compounds (VOC) has witnessed an enormous boost over the past decade, as this substance group has received broad attention regarding indoor air quality and disease screening. This review addresses the medical applications of proton transfer reaction-mass spectrometry (PTR-MS) in the fields of risk environment monitoring and diagnostic breath sample analysis. The major advantages of PTR-MS are its ability to perform rapid measurements as needed for the quick evaluation of screening samples, and even on-line VOC profile assessment. This may be of considerable importance in the investigation of rapidly changing air contamination patterns. Sources of contamination could be unveiled in operating theatres, post-anesthesia care units, and medical sterilization wards using PTR-MS. In the field of breath analysis, PTR-MS has been employed to investigate exhaled concentrations of isoprene, methanol, potential tumor markers, and volatile anesthetics. In conclusion, PTR-MS offers highly sensitive and rapid determinations of VOC profiles as compared to other methods of detection. PTR-MS therefore basically meets the needs of a screening method. The potential of directly mirroring serum concentrations of diverse substances in real-time makes breath analysis a highly promising field of research. [Copyright &y& Elsevier]