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The sixth of Hilbert’s famous 1900 list of twenty-three problems is a programmatic call for the axiomatization of physical sciences. Contrary to a prevalent view this problem was naturally rooted at the core of Hilbert’s conception of what axiomatization is all about. The axiomatic method embodied in his work on geometry at the turn of the twentieth-century originated in a preoccupation with foundational questions related with empirical science, including geometry and other physical disciplines at a similar level. From all the problems in the list, the sixth is the only one that continually engaged his efforts over a very long period, at least between 1894 and 1932.