Increasing evidence exists to support the presence of functional transient receptor potential vanilloid type 1 (TRPV1) channels in the brain, where these receptors are unlikely to be activated by high temperature and low pH. Here we review this evidence as well as the literature data pointing to the potential role of endovanilloid-activated brain TRPV1 channels not only in the supraspinal control of pain, body temperature, cardiovascular and respiratory functions and emesis, but also in anxiety and locomotion. This literature provides the first bases for the possible future development of new therapeutic approaches that, by specifically targeting brain TRPV1 receptors, might be used for the treatment of pain as well as affective and motor disorders.