This article examines the best seller of the Spanish Golden Age, the Libro de la oración y meditación (Book on Prayer and Meditation). Released in 1554 by the Spanish Dominican Luis de Granada, the prayer book went through over one hundred editions by 1600, read and reproduced by both Catholics and Protestants in English, French, German, Italian, Latin, Nahuatl, Spanish, and Zapotec. Despite its popularity, Granada’s book has prompted surprisingly little scholarly research. This paper examines several editions of the book (in English, French, Italian, and Spanish) highlighting what was changed while repackaging the book for new audiences. The paper suggests similarities and differences in popular piety across national, linguistic, and confessional lines. Tracing the evolution of Granada’s book helps to test the strength of confessionalization in Europe when applied to prayer, and it offers a standard lens for discerning the evolving shape of religious communities straddling reformations in different localities.