There is a requirement for economic evaluation of health technologies seeking public funding across Europe. Changes to the organisation and delivery of health services, including changes to health policy, are not covered by such appraisals. These changes also have consequences for National Health Service (NHS) funds, yet undergo no mandatory cost-effectiveness assessment. The focus on health technologies may have occurred because larger-scale service changes pose more complex challenges to evaluators. This paper discusses the principal challenges faced when performing economic evaluations of changes to the organisation and delivery of health services and provides recommendations for overcoming them. The five principal challenges identified are as follows: undertaking ex-ante evaluation; evaluating impacts in terms of quality-adjusted life years; assessing costs and opportunity costs; accounting for spillover effects; and generalisability. Of these challenges, methods for estimating the impact on costs and quality-adjusted life years are those most in need of development. Methods are available for ex-ante evaluation, assessing opportunity costs and examining generalisability. However, these are rarely applied in practice. The general principles of assessing the cost-effectiveness of interventions should be applied to all NHS spending, not just that involving health technologies. Advancements in this area have the potential to improve the allocation of scarce NHS resources.