Muscle nociception is mainly characterized by local tenderness and referred pain. The neurophysiological basis of muscle pain supports a role of sensitization mechanisms. From a clinical viewpoint, muscle pain is represented by the presence of myofascial trigger points (TrPs). Evidence suggests that TrPs are able to start a peripheral nociceptive mechanism and hence contributing to changes in the central nervous system. Several studies demonstrated that the referred pain elicited by TrPs reproduces the headache pattern in patients with tension-type headache (TTH), migraine, cervicogenic headache and, in some individuals, with cluster headache. In fact, sensitization of nociceptive pain pathways in the central nervous system due to prolonged nociceptive stimuli from TrPs seems to be responsible for the conversion of episodic to chronic TTH. In other headaches, TrPs may be able to stimulate the trigeminal nucleus caudalis and hence triggering a migraine or cluster headache attack. Proper treatment directed towards TrP inactivation has documented positive effects in individuals with these headaches; however, longitudinal studies are needed to further determine the role of TrPs in head pain.