This article presents and defends an integrated view of the placebo effect, termed “affective-meaning-making” model, which draws from theoretical reflection, clinical outcomes, and neurophysiological findings. We consider the theoretical limitations of those proposals associated with the “meaning view” on the placebo effect which leave the general aspects of meaning unspecified, fail to analyze fully the role of emotions and affect, and establish no clear connection between the theoretical, physiological, and psychological aspects of the effect. We point out that a promising (...) way to overcome these limitations is given by grounding the placebo effect on Peirce’s theory of meaning, in which the role of the meaning constitution and change is placed in logical and objective structures. We also show the connection between our theoretical proposal and the appraisal theory and integrate it with emotion regulation. (shrink)