Gender dysphoria is a term used to describe a person’s discontent with the assigned gender. Transgender persons may experience both internal and external stressors, which can impair their mental health. There is evidence of short-term and long-term benefits of gender-affirming medical care in multiple measures of mental health and psychological functioning. Gender dysphoria care is a challenging and multidisciplinary process, including a complex combination of psychological support and medical treatment. Available medical interventions include puberty-suppressing drugs, followed by cross-sex hormones and surgery. Gender confirmation surgeries include a series of genital and nongenital procedures required to make a masculine or feminine appearance. Different surgical approaches fulfill the person’s request at various levels. Based on present evidence and the latest guidelines, in this chapter, an overview of available medical care and mental health considerations in gender affirmation has been presented. Furthermore, ethical challenges of gender identity are highlighted, and future perspectives are elaborated.