This chapter first summarizes Response Surface Methodology (RSM), which started with Box and Wilson’s 1951 article on RSM for real, non-simulated systems. RSM is a stepwise heuristic that uses first-order polynomials to approximate the response surface locally. An estimated polynomial metamodel gives an estimated local gradient, which RSM uses in steepest ascent (or descent) to decide on the next local experiment. When RSM approaches the optimum, the latest first-order polynomial is replaced by a second-order polynomial. The fitted second-order polynomial enables the estimation of the optimum. This chapter then focuses on simulated systems, which may violate the assumptions of constant variance and independence. A variant of RSM that provab...