Chemical stressors such as environmental pollutants, metals, or persistent and nonpersistent chemicals are key components of the exposome, the set of all environmental exposures an individual is exposed to throughout their lifetime. These chemicals are found in the environment as combined mixtures and affect human physiology through several complex mechanisms. This chapter introduces the concepts of exposome and environmental mixtures in the context of population-based studies, discussing the challenges that incorporating the complex nature of environmental exposures as mixtures brings to the analyses. Of particular importance, the chapter introduces the several potential research questions that can be defined in the context of mixture studies in environmental epidemiology and that should be addressed for a comprehensive assessment of mixture-health associations.