The primary purpose of this chapter is to explore the viability of reasoning to the best explanation as a fundamental source of epistemically rational beliefs and a potentially useful weapon for use in responding to the skeptic. After making some important distinctions among various forms of explanationism, I’ll reach a somewhat pessimistic conclusion about the prospects for explanationist epistemologies solving fundamental epistemological problems. Explanationist epistemologies don’t seem to be fundamental sources of epistemically rational beliefs. As a result, fundamental epistemological problems, such as the threat of skepticism, are not solved by appeals to reasoning to the best explanation. We must look elsewhere for philosophically satisfying responses to these problems.