PET using [15O]H2O is a powerful tool for imaging coronary artery disease, being capable of quantifying myocardial blood flow and coronary flow reserve. Historically, its application in the clinic has remained limited due to technical and infrastructural difficulties and the lack of clinically useful images of myocardial blood flow. Recently, several of these difficulties have been overcome. This review provides a comparison of [15O]H2O with the other most widely used myocardial blood flow tracers, [13N]NH3 and 82Rb. In addition, an overview is given of tracer kinetic modeling of [15O]H2O data and of calculating parametric images of both myocardial blood flow and myocardial viability.