Long recognized as a defining feature of religion, prayer, paradoxically, has received only sporadic empirical attention. Recent investigations in the U.S. and the Netherlands have sought to address this gap by exploring the topic of prayer in programmatic fashions, significantly advancing the state of the art in terms of measurement of the practice of private prayer. The present paper first offers one way to integrate and expand the contemporary prayer literature using a conceptual analysis of religion. Second, challenges and possibilities associated with moving from this synthetic definition to neuroimaging work are examined within the framework of social cognitive neuroscience.