An important line of response to scepticism appeals to the best explanation. But anti-sceptics have not engaged much with work on explanation in the philosophy of science. I plan to investigate whether plausible assumptions about best explanations really do favour anti-scepticism. I will argue that there are ways of constructing sceptical hypotheses in which the assumptions do favour anti-scepticism, but the size of the support for anti-scepticism is small.