Acute pain of mild to moderate intensity is one of the problems most frequently encountered in primary care and emergency medicine and is a major reason of request for visit by patients. In recent years the focus has been more on the treatment of chronic pain, perhaps ignoring the negative impact of acute pain on quality of life and functional status of the patient, despite a growing number of evidence indicating the need to treat optimally also acute pain to avoid it prolongs in time. The remarkable progress achieved in the understanding of the physiological mechanisms of the nociceptive stimulus, as well as those common to biochemical inflammation and acute pain, highlighted the active and complex role of central nervous system in the genesis and maintenance of pain that from acute, if not promptly and adequately treated, can become chronic. In this article, after a brief introduction on the most recent advances on the transition from acute to chronic pain, we have focused on paracetamol, an analgesic drug widely used for over a century for its demonstrated efficacy and tolerability. Paracetamol that, thanks to a complex and not yet fully defined mechanism of action, certainly localized in the central nervous system, can have a significant role in the early treatment of acute pain aimed to reduce the risk of chronicization. Pharmacokinetic parameters and pharmacodynamic studies are outlined, as well as the latest acquisitions in terms of metabolism of this drug and the risks related to its misuse. Are also discussed the recommendations issued by scientific societies and recent articles that indicate paracetamol as the drug of first choice for mild to moderate pain in various clinical settings, such as post-operative pain, post-traumatic and osteoarticular diseases, alone or in association with weak opioids, in particular with codeine. Most recent findings about metabolism and analgesic effect of codeine and its metabolites are highlighted, and how, in combination with acetaminophen, there is an increase in analgesic efficacy without increasing side effects, offering the chance of obtaining a better pain control.