Pain is one of the most distressing symptoms that patients experience as they approach the end of life. Opioids remain the gold standard of care, but the need for alternative options continues to grow, especially in the face of opioid unresponsive pain or opioid side effects. Clonidine, a drug initially known as a nasal decongestant and anti-hypertensive, has shown promise through its depression of the sympathetic nervous system by inhibiting norepinephrine release. It has since shown potential as an analgesic post-operatively, helping to reduce overall opioid use while providing adequate pain relief. This systematic review aimed to collate and analyse the available literature on the use of clonidine as an analgesic for palliative care patients. A comprehensive literature search was performed on CENTRAL, SCOPUS, MEDLINE, EMBASE and ClinicalTrials.gov for studies assessing the use of clonidine as analgesia for patients under palliative care. Twelve studies involving 194 patients were included. All studies were either case reports or case series. Clonidine was used as both monotherapy and as an adjunct through a variety of delivery methods, including intrathecal, perineural, subcutaneous and transdermal. Clonidine has shown initial potential to provide adequate analgesia while reducing overall opioid usage. However, further research is required to form a stronger evidence base and gain further insight into its future role in this field. Further insight is also required into more easily accessible delivery, such as oral, subcutaneous and transdermal routes.