Religion has existed since the beginning of human society, before scientific advances were able to explain many natural phenomena. Hitchens holds that while religious belief was understandable in the early days of humanity, in the modern era it is foolish to believe in things for which there is no scientific evidence. He is especially critical of scientists who hold religious beliefs, both throughout history and today.

Hitchens describes the concept of deism, which was a popular school of thought during the Enlightenment. Enlightenment-era advances in science revealed a number of truths about the universe that had formerly been shrouded in mystery, and offered physical explanations for things that were originally believed to be the work of deities. Deists accepted science as a legitimate mechanism of understanding the world, but held that the complexity found in natural systems implied a conscious plan. They concluded that the universe must have been designed by some higher being, even if that being did not directly interfere with human life. Hitchens praises the deists for being rational thinkers for their time. The countless scientific discoveries made since the Enlightenment, though, make such a line of thinking irrational for contemporary humanity.

Hitchens focuses on astronomy and evolution as examples.