Gender-affirming treatment of transgender people requires a multidisciplinary approach in which endocrinologists play a crucial role. The aim of this paper is to review recent data on hormonal treatment of this population and its effect on physical, psychological, and mental health. The Endocrine Society guidelines for transgender women include estrogens in combination with androgen-lowering medications. Feminizing treatment with estrogens and antiandrogens has desired physical changes, such as enhanced breast growth, reduction of facial and body hair growth, and fat redistribution in a female pattern. Possible side effects should be discussed with patients, particularly those at risk for venous thromboembolism. The Endocrine Society guidelines for transgender men include testosterone therapy for virilization with deepening of the voice, cessation of menses, and increases of muscle mass and facial and body hair. Owing to the lack of evidence, treatment of gender nonbinary people should be individualized. Young people may receive pubertal suspension, consisting of GnRH analogs, later followed by sex steroids. Options for fertility preservation should be discussed before any hormonal intervention. Morbidity and cardiovascular risk with cross-sex hormones is unchanged among transgender men and unclear among transgender women. Sex steroid-related malignancies can occur but are rare. Mental health problems such as depression and anxiety have been found to reduce considerably following hormonal treatment. Future studies should aim to explore the long-term outcome of hormonal treatment in transgender people and provide evidence as to the effect of gender-affirming treatment in the nonbinary population.