The gambler’s fallacy is a cognitive error that presents itself in a variety of forms. It undermines a gambler’s understanding and fosters the belief that a win is more certain than it is. The therapeutic misconception is another well-known cognitive error that undermines a person’s understanding—in this case, a research participant’s—and fosters her belief that direct therapeutic benefit is more certain than it is. This article explores the parallels between them, revealing that the error inherent in the gambler’s fallacy is more akin to unrealistic optimism than it is to therapeutic misconception. The article then reviews the differences between unrealistic optimism and therapeutic misconception and concludes that unrealistic optimism poses a significant enough threat to informed consent for researchers to regularly screen participants in certain types of randomized clinical trials and exclude those who suffer from unrealistic optimism.