Toll-like receptors (TLRs) play an important role in the innate immune system, and recently, they have been shown to be involved in the regulation of blood pressure. The incidence of hypertension is higher in men, and it increases in postmenopausal women. In fact, premenopausal women are protected from cardiovascular disease compared with age-matched men, and it is well established that this protective effect is lost with menopause. However, the molecular mechanisms underlying this protection in women are unknown. Whether or not it could be related to differential activation of the innate immune system remains to be elucidated. This review focuses on (1) the differences between men and women in TLR activation and (2) whether TLR activation may influence the regulation of blood pressure in a sex-dependent manner.