The UK's National Institute for Health and Clinical Excellence (NICE), a world leader in health technology assessment (HTA), sits at the interface of a policy environment where everything is urgent and consensus between policy makers and stakeholders is sometimes difficult to attain. The majority of stakeholder challenges to NICE's use of HTA concern the interpretation of evidence and the methodological rules applied by the appraisal committees. We discuss the most significant issues: choice of comparators; evidence synthesis and indirect comparison; parameter selection, especially for the valuation of quality of life; extrapolation beyond clinical trial data; and the level of the cost-effectiveness threshold.