When considering disease etiology, we need to view the role of the environment along the continuum from health to disease for individuals because we know that there are complex interactions between genes, their molecular expression, and environmental factors over a person’s lifetime. We clearly have huge gaps in our knowledge along this continuum, and these gaps are natural opportunities for research. There are many factors to consider as we assess the relationship between environmental exposures over a lifetime. One factor is persistence of chemicals that “live” beyond their initial intended use. Another factor is the fact that “inert ingredients” are not really inert. “Low dose” is also another consideration. We need to understand the biological effect of low dose exposure and we should clearly define what they mean by low dose research. For example, are we measuring the administered dose, or the internal/circulating dose? There are new types of toxicity as well. For example, endocrine disruptors and engineered nanomaterials are significant classes of materials deserving significant research. Timing of exposure is a significant feature in characterizing toxicity. Environmental exposures can have a greater impact in early or later life-stages. Finally, mixtures of chemicals are an important consideration. Humans are always exposed to multiple chemicals. In short, we must remember that there is no such thing as “not exposed.” Everyone has been exposed to many and various environmental agents.