This review summarizes information concerning the association of the human flavin-containing monooxygenase 3 (FMO3) and human diseases. Human FMO3 oxygenates a wide variety of nucleophilic heteroatom-containing xenobiotics, including endogenous substrates and various clinically important drugs. In this article, the authors discuss the association of FMO3 with human disease, including: i) direct association of FMO3 genetic mutations to human genetic disease; ii) association of FMO3 genetic polymorphism to altered drug metabolism and, therefore, indirect association of FMO3 with drug therapeutic efficacy of human disease; and iii) the potential impact and/or effect of FMO3 transcriptional regulation during disease states. Even though many studies discussed for the latter two points are at a preliminary stage and require much more research to bring to a definite conclusion, the authors include these studies to stimulate general interest and invite further discussion.