We present a simple and general framework to simulate statistically correct realizations of a system of non-Markovian discrete stochastic processes. We give the exact analytical solution and a practical an efficient algorithm alike the Gillespie algorithm for Markovian processes, with the difference that now the occurrence rates of the events depend on the time elapsed since the event last took place. We use our non-Markovian generalized Gillespie stochastic simulation methodology to investigate the effects of non-exponential inter-event time distributions in the susceptible-infected-susceptible model of epidemic spreading. Strikingly, our results unveil the drastic effects that very subtle differences in the modeling of non-Markovian processes have on the global behavior of complex systems, with important implications for their understanding and prediction. We also assess our generalized Gillespie algorithm on a system of biochemical reactions with time delays. As compared to other existing methods, we find that the generalized Gillespie algorithm is the most general as it can be implemented very easily in cases, like for delays coupled to the evolution of the system, where other algorithms do not work or need adapt
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