This chapter introduces the major philosophical concepts, historical interpretations, and political, legal, and economic issues concerning the First Amendment, church-state relations, and religious liberty in the United States. It will address philosophical concepts such as natural religion, the nature of religious exercise, and the special status of religious liberty in the philosophy of law. It will then present historical developments from colonial America to modern Supreme Court cases concerning church establishments, religious toleration, religious dissent and minorities, religious tests, and the historical and jurisprudential meanings of “free exercise” and “establishment.” It will conclude with reflections on natural rights and religious liberty exemptions, originalist constitutional interpretations, corporate religious liberty, the economic origins of religious liberty, the separation of church and state, and contemporary challenges to religious liberty.