To protect the quality of water from toxic pollutants for the health of humans and the environment, two approaches are generally applied in the field of toxicology to predict the effects of pollutants and to monitor the toxic pollutants in water. Here we provide our perspective on state-of-the-art methods to develop water quality criteria and the use of molecular techniques for monitoring water quality. Emphasized is the recent development and application of cell-based assays and small fish model in toxicology research of water.