Controlling pain after major orthopedic surgery may be challenging, and it is related to delayed recovery, the development of chronic pain, and analgesic dependence. It is well known that effective postoperative pain control can reduce hospital stays by ensuring a more rapid rehabilitation,thereby decreasing the overall costs. Despite the development of analgesics, the use of opioids and their derivates remains the cornerstone of treatment for patients with acute moderate-to-severe pain in association with general or regional anesthesia. To reduce the risk of side effects and opioid addiction, considering the alarming epidemiological reports in relation to opioid abuse, combined analgesic methods are used, in addition to lower dosages or different forms of administration, such as transdermal administration. Fentanyl transdermal patches appear to be effective in controlling postoperative pain as part of multimodal analgesic regimens in knee and hip surgery, shoulder arthroplasty, traumatic fractures, and one-day surgery; this treatment has fewer associated side effects and can be safely used even in patients with renal impairment. It is also recommended for postoperative pain management in combination with a femoral-sciatic nerve block during foot and ankle surgery.