As rapid technological innovations continue to require the development of high-performance chemicals, we envision implementing a more interdisciplinary and precautionary approach in developing new chemical products by invoking smart chemical design to avoid the unwanted chemical properties of long-term environmental persistence, bioaccumulation and toxicity. We will develop chemical design criteria for a class of perfluoropolyether surfactant compounds, widely used for surface coatings, polymers and lubricants. Collectively, we will design candidate materials and assess how changes in the chemical structure of these model compounds reduce environmental persistence and toxicity without adversely affecting functional performance. The result will be a set of design criteria specific to this class of chemicals that integrates functional performance, biodegradation potential, environmental fate and biological toxicity information.