The effects of steroidal hormones on sexual desire and motivation are a question still under debate. This paper reviews up-to-date knowledge regarding physiological imprinting and activation by endogenous hormones of central nervous system areas involved in libido during intrauterine life and puberty. The endocrine environment probably continues to play a role during fertile life and the postmenopausal period, but this effect is often overridden by psychological and social factors. The impairment of sexual interest during estrogen-progestin treatment is an infrequent but relevant side-effect whose possible underlying mechanisms are discussed. Both endocrine and psychorelational elements may interact. From the biological point of view, androgen and oxytocin level modification and loss of estrogen fluctuations have been considered, but also the history of hormone-related mood changes could be a risk factor. On the psychological side, both the profound repercussions of the contraceptive choice and consequent responsibility, as well as the high value attributed to sexual experience are probably facilitating elements in the loss of libido under treatment.