Epidemiological studies have demonstrated that aspirin can protect against colorectal carcinogenesis. The mechanisms underlying this, however, are not fully understood. While the molecular mechanisms of aspirin and its inflammatory effects have been much discussed, my talk will focus on the direct effect of aspirin on the birth and death kinetics of tumor cells, and the consequences for cellular evolution. I will discuss data that show how aspirin modulates the division and death rate of colorectal cancer cells both in vitro and in vivo in a dose-dependent manner, and quantify how that influences the Darwinian fitness of the cells. Then the talk will discuss whether the observed magnitude of changes in cellular fitness are sufficient to significantly contribute to the epidemiologically observed protection. To investigate this, we constructed a class of mathematical models of in vivo evolution of advanced adenomas, parameterized it with available estimates, and calculated population level incidence. This model was used to predict modified incidence patterns if cellular kinetics were altered as a result of aspirin treatment. We found that changes in cellular fitness that were within the experimentally observed ranges could reduce the predicted advanced adenoma incidence by a sufficient amount to account for age incidence data in aspirin-treated patient cohorts.