We study instanton contributions to the superpotential of local F-theory compactifications which could potentially be used to engineer models of dynamical supersymmetry breaking. These instantons correspond to Euclidean 3-branes which form a threshold bound state with spacetime filling 7-branes. In certain cases, their contributions to the effective 4d superpotential can be determined in both perturbative string theory as well as directly via the topologically twisted theory on the 3-brane worldvolume, and in all cases we observe an exact match between these results. We further present an instanton generated Polonyi-like model, and characterize subleading corrections to the superpotential which arise from multi-instantons. We also study instanton contributions to 4d pure N=1 SU(N) gauge theory realized by a stack of 7-branes wrapping a rigid 4-cycle and find that there is a non-trivial contribution to the glueball superpotential from the single instanton sector. This correction is absent in the purely 4d theory and could conceivably be used either to stabilize moduli or to break supersymmetry.
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