Abstract. Given a Laurent polynomial f , one can form the period of f : this is a function of one complex variable that plays an important role in mirror symmetry for Fano manifolds. Mutations are a particular class of birational transformations acting on Laurent polynomials in two variables; they preserve the period and are closely connected with cluster algebras. We propose a higher-dimensional analog of mutation acting on Laurent polynomials f in n variables. In particular we give a combinatorial description of mutation acting on the Newton polytope P of f , and use this to establish many basic facts about mutations. Mutations can be understood combinatorially in terms of Minkowski rearrangements of slices of P , or in terms of piecewise-linear transformations acting on the dual polytope P * (much like cluster transformations). Mutations map Fano polytopes to Fano polytopes, preserve the Ehrhart series of the dual polytope, and preserve the period of f . Finally we use our results to show that Minkowski polynomials, which are a family of Laurent polynomials that give mirror partners to many three-dimensional Fano manifolds, are connected by a sequence of mutations if and only if they have the same period.