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A generalized quadrangle is a point-line incidence geometry Q such that: (i) any two points lie on at most one line, and (ii) given a line ℓ and a point P not incident with ℓ, there is a unique point of ℓ collinear with P. The finite Moufang generalized quadrangles were classified by Fong and Seitz [Invent. Math. 21 (1973), 1-57; Invent. Math. 24 (1974), 191-239], and we study a larger class of generalized quadrangles: the antiflag-transitive quadrangles. An antiflag of a generalized quadrangle is a nonincident point-line pair (P, ℓ), and we say that the generalized quadrangle Q is antiflag-transitive if the group of collineations is transitive on the set of all antiflags. We prove that if a finite thick generalized quadrangle Q is antiflag-transitive, then Q is either a classical generalized quadrangle or is the unique generalized quadrangle of order (3, 5) or its dual. Our approach uses the theory of locally s-arc-transitive graphs developed by Giudici, Li, and Praeger [Trans. Amer. Math. Soc. 356 (2004), 291-317] to characterize antiflag-transitive generalized quadrangles and then the work of Alavi and Burness [J. Algebra 421 (2015), 187-233] on “large” subgroups of simple groups of Lie type to fully classify them.