© 2018 Springer Publishing Company. People may have a visibly different appearance due to various causes, such as congenital conditions, injury, disease, or medical treatment. Some individuals with a visible difference experience social anxiety and isolation, body image dissatisfaction, shame and self-stigma, psychological trauma, and challenges managing their condition. In this article, we synthesize the relevant literature and present the theoretical rationale for the application of Acceptance and Commitment Therapy (ACT), a third-wave behavioral therapy combining mindfulness skills and value-driven action, to those experiencing distress relating to an unusual or altered appearance. We also outline how ACT may be tailored to the specific considerations of this population and recommend next steps in researching its acceptability and clinical effectiveness.