Non-invasive disease diagnosis with high accuracy is a vital element in healthcare. Detecting the volatile metabolites in breath, body, and wastes via an electronic nose (E-nose) has been demonstrated as a practical, low-cost, and accurate approach to diagnose diseases. This chapter introduces the history and research of disease-related volatolomics since 1971, the developments of E-nose technology, mainly in the past two decades, for healthcare applications, and the E-nose technology in healthcare. The chapter contents, including olfaction inspired working principle, advanced sensory units as olfactory receptors, data analysis methods mimicking the human brain, various applications in healthcare, are elaborated, as much information as possible, from a bird vision to the whole field, instead of going into them deeply. If the readers want to know more information in detail, the cited references had given perfect guidance to what you want. In addition, the future perspectives but not limited to those items, are given to our best knowledge, which might be valuable suggestions in developing orientations.