Per- and polyfluoroalkyl substances (PFAS), also known as 'forever chemicals', are of high concern for human and ecosystem health. PFAS were first synthesised and developed in the late 1930s, and are now commonplace in many everyday objects, such as frying pans, food packaging and cleaning products. Due to their long half-life, these chemicals remain at high concentrations in both the environment and within exposed organisms, where they have toxic effects. Several model and animal models have been developed to help determine the deleterious effects of PFAS, which has led to the identification of multiple pathways and mechanisms that are affected or presumed to be affected. In this Review, we present an overview of PFAS and discuss possible effects on humans and wildlife. We discuss the pros and cons of various vertebrate and invertebrate model systems that have been used to study PFAS. Finally, to further address these chemicals in the future, we discuss different approaches to removing PFAS from the environment.