Hope was central to cancer control in twentieth-century America. Physicians placed great store in its power to persuade people to seek medical help as early as possible in the development of the disease, when it was most amenable to treatment; to maintain patients' loyalty through what could be a long, painful and uncertain course of therapy; and to encourage doubts about alternative healers. Some also argued that hope could have beneficial therapeutic and psychological effects for patients. However, we know very little about its meanings for the public. Focusing on a large collection of letters written to the Food and Drug Administration in the 1950s concerning an anti-quackery campaign, this article explores how men and women responded to the competing messages of hope promoted by orthodox cancer organizations and by alternative healers. It asks: What did hope mean to such men and women? How did they construct this meaning? How did they decide which treatments were hopeful and which were not? And, how did they use hope to imagine the social world of cancer? In short, this article explores the vernacular meanings, epistemologies, and imaginative uses of hope among Americans in the mid-twentieth century.