Abstract The problem of optimal experimental design (OED) for parameter estimation of non-linear dynamic systems is considered. It is shown how this problem can be formulated as a dynamic optimization (optimal control) problem where the performance index is usually a scalar function of the Fisher informatioin matrix. Numerical solutions can be obtained using direct methods, which transform the original problem into a non-linear programming (NLP) problem via discretizations. However, due to the frequent non-smoothness of the cost functions, the use of gradient-based methods to solve this NLP might lead to local solutions. Stochastic methods of global optimization are suggested as robust alternatives. A case study considering the OED for parameter estimation in a fed-batch bioreactor is used to illustrate the performance and advantages of two selected stochastic algorithms.