Androgen insensitivity arises from target tissue resistance to androgens. Androgen insensitivity syndrome (AIS) is the most common specific etiology of 46,XY differences of sex development. It is a result of the failure of androgens to act via the androgen receptor (AR). The phenotype is variable, from a female phenotype in complete AIS to a male phenotype with gynecomastia or infertility in minimal AIS, depending on the residual androgen receptor activity. More than 600 different androgen receptor mutations have been reported in AIS, and they have been identified in all eight exons of the gene. More recently, several mutations in the 5′ untranslated region of the AR gene have also been described, which impair AR function by reducing AR protein levels. The treatment consists of counseling, psychosocial support, endocrine therapy, and surgery. Both the type of hormonal substitution and gonadectomy or its timing are still controversial.