Transsexualism is a sexual identity disorder distinguished by the extreme conviction of belonging to the opposite sex with a total disharmony in the original sex. Diagnosis is established when patients respond to three criteria (DSM-IV): 1) Desire to live and to be accepted as members of opposite sex; 2) Presence of sexual identity disorder for minimal two years; 3) Lack of mental disease or chromosomal anomalies. When diagnosis is confirmed, hormonal treatment can be started and so, improve the secondary sexual characters of selected sex. For patients F–M, treatment is composed of testosterone, most commonly esters of testosterone. For patients M–F, treatment consists of estrogens. These estrogens are frequently associated to an anti-androgen (cyproterone acetate) in the pre-reassignment phase. Avoiding the hepatic way, transdermal form is recommended. Hormonal treatments are not devoid of secondary effects: the most frequent one is venous thromboembolism. Considering contraindications and potential complications, each patient must be selected carefully. The endocrinological follow-up is essential and necessary.