Despite published guidelines and educational programs on the assessment and treatment of cancer-related pain, in any stage of oncological disease, unrelieved pain continues to be a substantial worldwide public health concern either in patients with solid and haematological malignancies. The proper and regular self-reporting assessment of pain is the first step for an effective and individualized treatment. Opioids are the mainstay of analgesic therapy and can be associated with non-opioids drugs such as paracetamol or non-steroidal anti-inflammatory drugs and to adjuvant drugs (for neuropathic pain and symptom control). The role and the utility of weak opioids (i.e. codeine, dihydrocodeine, tramadol) are a controversy point. Morphine has been placed by World Health Organization on its Essential Drug List. In the comparative study with other strong opioids (hydromorphone, oxycodone), there is no evidence to show superiority or inferiority with morphine as the first choice opioid. Oral methadone is a useful and safe alternative to morphine. Methadone presents the potential to control pain difficult to manage with other opioids. although the oral route of opioid administration is considered the one of choice, intravenous, subcutaneous, rectal, transdermal, sublingual, intranasal, and spinal routes must be used in particular situation. Transdermal opioids such as fentanyl and buprenorphine are best reserved for patients whose opioid requirements are stable. Switching from one opioid to another can improve analgesia and tolerability.