Tobacco science bas been analytically focused for many years, yielding what is found in smoke and at what levels. Of course, we have gone beyond the traditional T, N, and CO to Hoffmann analytes and further in this first wave of tobacco science. However, these efforts only clue us to the levels of constituents in smoke. Recently, we have moved beyond analytical measurements to exposure, bringing us to the second wave of tobacco science -what biomarkers are observed when laboratory surrogates (i.e., in vitro) and animals (i.e., in vivo ) as well as humans are exposed to smoke? While these biomarkers of exposure are numerous, fairly well understood and readily measurable, we need to address the effects that these exposures create in these test systems and organisms. Current activities around understanding how these exposures manifest as effects leads us to the third wave of tobacco science - biomarkers of effects and ultimately risk. This presentation takes us through the three waves of tobacco science as it relates to, our increased understanding of the risks inherent in tobacco. We also briefly discuss how these waves are expected to be integral in upcoming regulatory scenarios.