Some authors have proposed an updating of the therapeutic recommendations for some kinds of pain, such as musculoskeletal, post-traumatic and post-surgical pain for which a multimodal approach is being increasingly considered. With regard to this, an association of analgesics belonging to different pharmacological classes becomes an important option, given that analgesic efficacy can be ensured using lower dosages of single components, improving the tolerability of the drugs. The fixed combination of paracetamol (325 mg) and tramadol (37.5 mg) has a precisely dose ratio to obtain an additive analgesic effect, improving both the analgesic efficacy, which is more stronger and complete, and the duration of the action, guaranteeing a quick analgesic effect over time. A wide international literature exists for this association. This review considers particularly 15 studies. In nine of them, all double-blind, the duration of treatment was 1-10 days and, in total, 2 537 patients were admitted, affected by acute painful flares of chronic-degenerative pathologies, trauma or subjected to surgery. The mean daily dose of paracetamol/tramadol most frequently used was 4.3-4.5 tablets/day. Rigorous studies were conducted also for chronic pain; in the 6 studies considered the duration of treatment was 4-13 weeks and a total of 1 890 patients, affected by chronic musculoskeletal pain, were admitted. The mean daily dose of paracetamol/tramadol was between 3.5 and 4.2 tablets/day, showing itself to be constant and independent of the disease considered. In conclusion, the fixed association paracetamol/tramadol is a new therapeutic option, particularly useful in mild-moderate pain where paracetamol is inadequate.