In the present article, we examine the basic and applied aspects of the social psychology of religious worldview defense; that is, how people react in terms of negative affective reactions toward extremely antireligious statements that threaten their religious beliefs and/or may violate their views of how one should communicate about religious issues. An Internet study (N = 1,529) and a laboratory experiment (N = 151) provide evidence for the hypothesis that salience of personal uncertainty concerns may lead people to react with more negative affective reactions toward extremely negative statements about religion, particularly when people are inclined to think of personal uncertainty as an emotionally threatening experience and when they are strongly religious. Implications for the psychology of religion and the social psychology of uncertainty and worldview defense are discussed.