Effective treatment of postoperative acute pain, together with early mobilization and nutrition, is one of the perioperative strategies advocated to improve surgical outcome and reduce the costs of hospitalization. Moreover, adequate pain control reduces perioperative morbidity related to surgical stress and can also prevent the incidence of chronic postoperative pain syndromes, whose treatment is still a challenge. The choice of the most appropriate analgesics depends not only on the drug class, but also on the most suitable route of administration, the best dosage for that route, and unique limitations and contraindications for every patient. In the present review, a comprehensive analysis was performed on the different routes of administration of acute postoperative pain medications and their indications and limitations, focusing on recent evidence and international recommendations.