This review aims to demonstrate the relevance that medicinal plants and their promising results have in prevention and treatment of pain. The neurophysiological bases of pain have been analyzed and the potential mechanisms of action have been proposed, it has also been determined that the main experimental models used for the evaluation of the analgesic potential are: acetic acid-induced writhing test, formalin test, hot-plate test, capsaicin-induced nociception, cinnamaldehyde-induced nociception, glutamate-induced nociception, tail–flick test and tail immersion test. There are countless medicinal plants with potential analgesic activity, in some of them main responsible compounds for the activity are flavonoids (vitexin, quercetin, naringenin, astragalin, eupatilin), alkaloids (scotanamine B, bullatine A, S-(+)dicentrine, stephalagine, lappaconitine), terpenoids (p-cymene, thymol, menthol, citronellol, myrcene, carvacrol, linalool) and saponins (siolmatroside I, cayaponoside D, cayaponoside B4, cayaponoside A1); however, all studies have only been carried out up to pre-clinical stages. Therefore, it is recommended to carry out kinetic studies of the most remarkable natural compounds, evaluate mixtures of active compounds for diminishing doses to avoide possible side effects, and continue with clinical studies of medicinal plants whose safety has already been reported.