The foundation of the Renaissance/Reformation Collection was established with the acquisition of the Marco Heidner Collection in 1966. That fall, BYU president Ernest L. Wilkinson and vice president Earl C. Crockett approved the purchase of the collection of 15th- and 16th-century books for the BYU library. Based on the strength of the Heidner Collection, coupled with increased student and faculty expertise in this area, the university then directed the library to concentrate some of its collecting efforts on the Renaissance and Reformation.

For the Renaissance period, this collection emphasizes European diplomacy, political treatises, French political pamphlets from 1550 to 1650 (2,500 in total), and major editions of classical Greek and Latin authors. Associated with the latter, Special Collections has chosen to emphasize the collecting of incunabula (450 titles) and collections of works printed by Aldus Manutius and his heirs in Venice (600 titles); Henri Estienne, Robert Estienne, and Henri Estienne II in Paris and Geneva (500 titles); Simon de Colines in Paris (300 titles); Badius Ascensius of Paris (60 titles); the Giunta family of printers in Florence (140 titles plus 360 printed Laws of the City of Florence); Froben of Basel (120 titles); and Christopher Plantin of Antwerp (225 titles).

For the Reformation period, the library collects works written by the major religious figures of the time, including Martin Luther (95 separate pamphlets), Philip Melanchton, John Calvin, John Wesley, Savonarola, Erasmus, Thomas More, etc. In addition, the library collects major and minor religious and political treatises and pamphlets representative of the work of Reformation thinkers.