For the last few decades intense scientific research has been placed on the relationship between trace substances found in exhaled breath such as volatile organic compounds (VOC) and a wide range of local or systemic diseases. Although currently there is no general consensus, results imply that VOC have a different profile depending on the organ or disease that generates them. The association between a specific pathology and exhaled breath odor is particularly evident in patients with medical conditions such as liver, renal or oral diseases. In other cases the unpleasant odors can be associated with the whole body and have a genetic underlying cause. The present review describes the current advances in identifying and quantifying VOC used as biomarkers for a number of systemic diseases. A special focus will be placed on volatiles that characterize unpleasant breath 'fingerprints' such as fetor hepaticus; uremic fetor; fetor ex ore or trimethylaminuria.