The wide-spectrum chemical characterization of human breath has allowed over the years the identification of several diseases-related volatile biomarkers (both chronic and oncologic diseases). Human breath composition, both in healthy subjects and in ill patients, is multifactorial and reflects the composition of the volatile fraction in the bloodstream and in respiratory tract of the human body, as well as the metabolic processes that regulate cellular functioning. Despite breath analysis might appear full of pitfalls and limitations, it has proven to be a promising diagnostic tool for early diagnosis of both chronic and oncologic diseases. Therefore, further research in the field is needed to fill the existing knowledge gaps and to continue exploring the complex matrix of human breath volatome in the view of accrediting breath analysis as a reliable and innovative diagnostic tool for prevention of human diseases with high mortality rate.