It has been known for a long time that instanton effects control the large order behavior of the perturbation series in quantum mechanics and gauge theories. I present a study of this connection in the context of matrix models in 1/N-expansion and topological strings. I will show how to compute the one-instanton corrections for a generic matrix model. Due to a recent matrix model inspired formalism for the topological string amplitudes on local Calabi-Yau manifolds, this can be used to compute nonperturbative effects in topological string theory and make predictions about the asymptotics of the string perturbation series. I discuss various cases where our predictions can be tested, yielding spectacular agreement with the asymptotics extracted by standard numerical methods.