Cancer-related pain is present in 51% of patients at various stages of the disease, and the incidence increases up to 74% in advanced and terminal stages. The World Health Organization proposed and issued very simple guidelines for the pharmacologic treatment of cancer-related pain. According to the guidelines, opioid analgesics are the mainstay of analgesic therapy, and the first choice for drug administration is considered to be the oral route. However, in some clinical situations, the oral route is not feasible, and analgesic drugs consequently have to be administered via an alternative route. For example, this is the case when the patient presents vomiting, bowel obstruction, severe dysphagia, mental confusion and when the opioid dose has to be increased drastically in order to achieve adequate pain control. This review of the literature is aimed at describing the indications, the limits and the main aspects of the pharmacokinetics and pharmacodynamics relative to the alternative routes of administration of opioids most commonly used in clinical practice. Sublingual, rectal, subcutaneous, intravenous, transdermal and spinal administration routes are examined.