Over the past three decades, since the creation of the Mind and Life Institute in the 1980s under the auspices of the Dalai Lama and the neurobiologist Francisco Varela, a series of conferences have introduced the idea of a convergence between Buddhism and neuroscience. Neuroscientists have been particularly interested in the possible neural correlates of Buddhist meditation, and their experiments have contributed to the current popularity of Mindfulness and derived techniques, such as “Mindfulness-Based Stress Reduction” (MBSR). Because of media attention and a desire to reach consensus, however, points of divergence have been ignored or downplayed, and the conversation has been limited to certain forms of Buddhist thought and practice. The time has come to move “beyond the hype” and to engage in a broader and more critical discussion. In the recent past, Western advocates of Buddhist modernism have argued for a need to “naturalize” Buddhism, that is, to rid it from allegedly peripheral elements such as karma, cosmology, ritual, and myth, in order to better focus on the philosophical and meditative contents of the Buddha’s teaching. What philosophically-minded scholars would see as a long-overdue purification process, however, others may see as an impoverishment, a form of reductionism. The same debate has been rehearsed, in one way or another, for more than one century. What gives it a renewed urgency is the advent of neuroscience. In particular, its reduction of mind to brain—of mental events to physical phenomena—presents Buddhism with a radical challenge. This paper explores this challenge and examines the question of the naturalization of Buddhism using a two-pronged approach: a critical assessment of naturalism; and a reevaluation of the most recent forms of Buddhist modernism (and postmodernism), including the extraordinary success of Mindfulness. It argues for a more balanced and encompassing approach that would extol the richness of the Buddhist tradition.