Like any other specialty, palliative care needs a scientific foundation on which to base its practice. Research in palliative care is particularly difficult because of the characteristics of the patient population under study (e.g. advanced disease, poor performance status and limited prognosis). The aim of this paper was to highlight the challenges of recruitment into clinical trials in palliative care. Information on all patients treated at a specialist cancer centre who were referred for consideration of entry into any one of 23 clinical trials in palliative care was collected prospectively over 4 years to determine factors that influence patients to accept or reject entry into a study. Of the 1206 patients referred, 558 (46%) met the entry criteria. Of these, 362 (30%) agreed to enter and 248 (21% of all those referred) completed the study. Thus, 65% of all eligible patients were entered into trials but only 44% of these completed the study. The relatively high percentage of patients entered probably reflects the site (a cancer centre with a high research profile) and is not typical of other palliative care centres or hospices. The most common reasons given for unwillingness to participate were a wish to defer to a later date, a deterioration in condition, distance from home to hospital, a lack of interest, transfer to another unit, inability to give consent and family objection. In order to maximise patient accrual into trials in palliative care, studies should be designed to suit the patient population under study (e.g. be of short duration with realistic entry criteria) and not necessarily mirror the trial methodology of therapeutic trials in oncology.