An unusual physical appearance, of any nature, including giant congenital melanocytic nevi, nasolabial clefts, and burns, is a visible difference (VD). It can have multiple possible consequences on an affected individual, including appearance-distress. Social appearance anxiety (SAA) constitutes one of its main symptoms. While offering an in-depth analysis of the impact of a VD on the individual and his social environment, this chapter presents a new perspective on the matter. Examining rigorously a patient’s past and current reactions, in specific contexts, enables a global and sharp understanding of the mechanisms that develop and maintain their suffering over time. It allows a personalized and efficient therapeutic plan to be elaborated, guided by the global theory of the patient and multiple functional analyses. The care relies on a precise methodology using classic cognitive behavioral therapy tools and techniques, as well as those specific to SAA in VD.