COVID-19 has generated a new and distinctive focus on the use of human challenge studies, also known as controlled human infection trials . The first such trial was authorised in England in February 2021 . Although vaccines are now available for COVID-19, there remain multiple deficits in knowledge in respect of treatment and prevention of the infection and a powerful impetus for solutions given the level of its global morbidity and mortality . Thus, there are potent incentives for unorthodox acceleration of medical knowledge but against these must be balanced ethical and pragmatic considerations . This editorial adds to the literature on such issues by reflecting on the ethical principles that are applicable and identifying the arguments that have been mustered for and against human challenge studies in relation to COVID-19 . It argues that, given the limited state of knowledge about the diverse and longer term risks from contraction of COVID-19, considerable care needs to be devoted to any assessment of the appropriateness of human challenge trials to test treatments for the disease or measures to prevent contracting the virus.