Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.