To what extent can one’s mind promote direct changes to the body? Can one’s beliefs about the body become a physical reality, without mediating effects from behaviors? Specifically, can medical symptoms and the course of a disease be directly affected by a person’s mindset about the illness? There is a vast literature about placebo and nocebo effects, that promote physical changes by creating the expectation of a change through a primer (for example, a fake pill). Placebos, however, often imply deception, or at least ambiguity, to be effective. The concept of Illness Expectation describes the expectations, both implicit and explicit, that a person who has received a diagnosis makes about the course of the disease. It can be characterized by different degrees of rigidity, and it is argued here that these expectations can ultimately lead to changes in the disease progression. These changes may happen through behavior modifications, or through a non-behavioral pathway, which may deserve exploration efforts from the scientific literature.