This chapter takes a critical psychology approach to reviewing research on psychological distress among people with variations of sex characteristics. The focus is on depathologizing emotional distress and developing affirming and empowering approaches to healthcare. Affirming approaches to psychosocial healthcare can be undertaken by health professionals who have enough knowledge about intersex, diverse sex development, or variations of sex characteristics to be able to support positive adaptation to bodily variation and facilitate non-stigmatizing talk about the experience of living with a diagnosis. There is room for significant development here, particularly research addressing psychosocial well-being in ways that are non-medicalized and culturally relevant in diverse global regions.