Abstract: In recent years, a renewal of interest in Lucretius' De Rerum Natura has focused almost exclusively on questions of atheism, later literary imitations, and the poem itself as a source of materialist philosophy. This dissertation takes a different approach to the poem's reception in the Renaissance, demonstrating how Lucretius---in spite of his bad reputation---became a radical guide for the transmission and renovation of ancient wisdom and a model for rethinking the character and development of humanism from the late Quattrocento to the age of Isaac Newton. Chapters 1 and 2 explore the historical invention of Lucretian influence. If De Rerum Natura was discovered in 1417 after hundreds of years of oblivion its ancient authority in the works of poets such as Virgil and Ovid was another belated revelation. Using the poetry and philology of Angelo Poliziano, the logic of Peter Ramus and Gabriel Harvey, and the scholarship of Aby Warburg, I demonstrate how ancient patterns of influence were activated and given new expression through the history and transformation of humanistic practices. Chapters 3, 4, and 5 look at various aspects of the poet's influence on the idea of tradition itself---from the philological reconstruction of the text in the sixteenth century to the works of Michel de Montaigne, Francis Bacon and Pierre Gassendi. Here, I show how an open-ended, contingent, and evolving idea of texts and history crept into Renaissance thinking about the nature, ontology, and uses of tradition. For humanists of the sixteenth and seventeenth centuries the Epicurean poet was not merely an influence, but a theorist of influence, transmission, and the fortunes of knowledge. Chapters 6 and 7 consider the project of Lucretius' poetic renovation of Greek wisdom in the light of seventeenth-century debates about the ancients and moderns and the relation between philosophy and literature. Looking to the works of Henry More, Ralph Cudworth, Isaac Newton, and Jonathan Swift, I show how the literary and materialistic dynamics of the poem continued to shape the construction of Renaissance ideas of history (and, ultimately, our own idea of the 'Renaissance') even as humanistic models of knowledge gradually gave way to scientific and mathematical ones.