The peripheral apparatus of muscle pain consists of nociceptors that can be excited by endogenous substances and mechanical stimuli. Histologically, the nociceptors are free nerve endings supplied by group III (thin myelinated) and group IV (nonmyelinated) afferents with conduction velocities less than 30 m/s. At the molecular level, nociceptors have receptors for algesic substances, such as bradykinin, serotonin, and prostagladin E2. The purinergic receptors and tetrodotoxin-resistant sodium channels might be new important targets for the treatment of muscle pain. Algesic substances (capsaicin, bradykinin, serotonin, potassium chloride, and hypertonic saline) and other stimuli (ischemia, strong mechanical stimuli, and electrical stimuli) have been shown to induce nociception from muscle in animals and muscle pain in humans. Muscle nociceptors can be sensitized to chemical and mechanical stimuli. Contrary to a former belief, the sensitization is not an unspecific process; rather, it is caused by endogenous algesic substances binding to highly specific receptor molecules in the membrane of the nociceptive ending. For example, animal studies showed that serotonin sensitizes muscle nociceptors to chemical and mechanical stimuli. Later, human studies showed that serotonin combined with bradykinin induces muscle hyperalgesia to pressure. The sensitization process by endogenous substances that are likely to be released during trauma or inflammatory injury is probably the best established peripheral mechanism for muscle tenderness and hyperalgesia.