Are knowledge and belief pivotal in science, as contemporary epistemology and philosophy of science nearly universally take them to be? I defend the view that scientists are not primarily concerned with knowing and that the methods of arriving at scientific hypotheses, models and scenarios do not commit us having stable beliefs about them. Instead, what drives scientific discovery is ignorance that scientists can cleverly exploit. Not an absence or negation of knowledge, ignorance concerns fundamental uncertainty, and is brought out by retroductive (abductive) inferences, which are roughly characterised as reasoning from effects to causes. I argue that recent discoveries in sciences that coped with under-structured problem spaces testify the prevalence of retroductive logic in scientific discovery and its progress. This puts paid to the need of finding epistemic justification or confirmation to retroductive methodologies. A scientist, never frightened of unknown unknowns, strives to advance the forefront of uncertainty, not that of belief or knowledge. Far from rendering science irrational, I conclude that catering well for the right conditions in which to cultivate ignorance is a key to how fertile retroductive inferences (true guesses) arise.