As a bridge between theory and experimentation, computer simulation has become a powerful tool in scientific research. It provides not only preliminary validation of theories, but also guidelines for empirical experiments. Plant breeding is to develop superior genotypes with available genetic and non-genetic resources, during which selecting the best breeding strategy would maximize genetic gain and achieve cost-effectiveness. Computer simulation can establish the breeding process in silico and identify candidates of the optimum combination of various factors, which can then be validated empirically. Insights gained from empirical studies, in turn, can be further incorporated into computer simulations. In this review, we discussed the application of computer simulation in different aspects of plant breeding. First, we briefly summarized the history of plant breeding and computer simulation, and how computer simulation can be used to facilitate the breeding process. Next, we partitioned the utility of computer simulation into different research areas of plant breeding, including breeding method comparison, genetic mapping, gene network and genotype-environment interaction simulation, and crop modeling. Then we discussed computational issues involved in the simulation process. Finally, the application of computer simulation in the future was discussed.