Background: Opioids are a range of molecules which bind to opioid receptors. They have variable effects on the different opioid receptors and can have actions on a range of non-opioid receptors. Clinically, opioids are often used in the management of pain caused by cancer. Although they can provide effective symptom control, they can cause a range of side effects. Their effect on immunity is a potential covert side effect which is often not considered or measured in the clinical setting. This chapter will discuss about opioids, their differences, opioid use in patients with cancer, and effects of opioids on the immune system. Animal, human, and clinical studies assessing anti-cancer immunity will also be covered. Methods: In this review article, the keywords in the threads, opioids AND cancer/neoplasia AND immunity/immune, were searched for in PubMed with no limits applied. This included the different opioid names in the opioid thread morphine, tramadol, fentanyl, buprenorphine, and oxycodone. Results: Opioids are a heterogenous group of drugs with different immune effects. They can influence immune function by having direct effects on immune cells (this is through actions primarily on the mu opioid receptors and Toll-like receptor-4) as well as via indirect effect via the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Animal studies have correlated the immune effects of opioids on cancer-related outcomes with immunosuppressive opioids such as morphine increasing tumor growth in these models and immunoenhancing opioids such as tramadol being associated with less tumor growth. Human cancer surgical studies have shown mixed results to cancer-related outcomes using opioid-sparing techniques. There are no such studies in nonsurgical patients on long-term opioids, which are limited to measuring immune activity rather than clinical endpoints. Conclusions: Different opioids influence anti-cancer immunity in different ways. However, how these effects impact on the patient in terms of cancer progression and survival is not clear. Opioids should continue to be used in patients with cancer, and further study on their effects on immunity with hard clinical endpoints is needed.