What does it mean to say that mutation is random? How does mutation influence evolution? Are mutations merely the raw material for selection to shape adaptations? The author draws on a detailed knowledge of mutational mechanisms to argue that the randomness doctrine is best understood, not as a fact-based conclusion, but as the premise of a neo-Darwinian research program focused on selection. The successes of this research program created a blind spot - in mathematical models and verbal theories of causation - that has stymied efforts to re-think the role of variation. However, recent theoretical and empirical work shows that mutational biases can and do influence the course of evolution, including adaptive evolution, through a first come, first served mechanism.This thought-provoking book cuts through the conceptual tangle at the intersection of mutation, randomness, and evolution, offering a fresh, far-reaching, and testable view of the role of variation as a dispositional evolutionary factor. The arguments will be accessible to philosophers and historians with a serious interest in evolution, as well as to researchers and advanced students of evolution focused on molecules, microbes, evo-devo, and population genetics.