hTere has been a paradigm shitf in medicine away from tradition, anecdote and theoretical reasoning from the basic sciences towards evidence-based medicine (EBM). In palliative care however, statistically signiifcant beneifts may be marginal and may not be related to clinical meaningfulness. hTe typical treatmentvs. placebo comparison necessitated by ‘gold standard’ randomised controlled trials (RCTs) is not necessarily applicable. hTe complex multimorbidity of end of life care involves considerations of the patient’s physical, psychological, social and spiritual needs. In addition, the field of palliative care covers a heterogeneous group of chronic and incurable diseases no longer limited to cancer. Adequate sample sizes can be diffcult to achieve, reducing the power of studies and high attrition rates can result in inadequate follow up periods. hTis review uses examples of the management of cancer-related fatigue and death rattle (noisy breathing) to demonstrate the current state of EBM in palliative care. hTe future of EBM in palliative care needs to be as diverse as the patients who ultimately derive benefit. Non-RCT methodologies of equivalent quality, validity and size conducted by collaborative research networks using a ‘mixed methods approach’ are likely to pose the correct clinical questions and derive evidence-based yet clinically relevant outcomes.