Summary Successfully delivering medical care and acquiring and disseminating the new knowledge that underpins clinical advance requires dealing with a number of both theoretical and organizational issues that may impede progress. Firstly, we have to move beyond the idea that biology and medicine are synonymous, and realize that tropes such as 'bench to bedside' or 'translational' frequently do not capture the way medical advance occurs. Medicine is more engineering than science, and the constraints imposed by society and economics, as well as historical models of working, may all delay improvements in healthcare delivery. Secondly, the generation of new ideas is influenced by the social organization and financial underpinning of science. Comparisons with other areas of science and technology suggest that medical science is dysfunctional and lacking in genuine innovation, particularly when cost is factored in as a key denominator. There are reasons to believe that matters are getting worse, and that the climate for revolutionary discovery is less supportive in both academia and industry than it was in the mid-to-late twentieth century. Thirdly, healthcare delivery is subject to a number of factors that limit cheap and effective care. These include payment systems that encourage unnecessary care, self-interest by medical guilds and insurers, and regulators that seek to limit new ways of working. Finally, there is also a striking failure to study and understand medical competence, how we educate doctors and other clinicians, and how technology might help to reduce costs.