The article discusses the use of molecular replacement (MR) with the Phaser program to solve structures of protein complexes. MR involves placing a search model rigidly in the asymmetric unit of a target crystal to minimize the difference between the calculated and observed structure factors. The success of MR depends on the fraction of the asymmetric unit with suitable models and the root mean square deviation (RMSD) between the model and the target structure. Maximum-likelihood MR functions, implemented in Phaser, improve the success rate by using more discriminating rotation and translation functions, which can incorporate partial structure information. The 'tree search with pruning' algorithm in Phaser iteratively links anisotropy correction, model generation, rotation function, translation function, packing function, and rigid-body refinement to solve complex asymmetric units. The article presents four case studies to illustrate how Phaser can be used effectively in standard automated MR mode and how modifications to the automated search strategy can be made for problematic cases, such as multiple copies of the same component or varying B-factors.The article discusses the use of molecular replacement (MR) with the Phaser program to solve structures of protein complexes. MR involves placing a search model rigidly in the asymmetric unit of a target crystal to minimize the difference between the calculated and observed structure factors. The success of MR depends on the fraction of the asymmetric unit with suitable models and the root mean square deviation (RMSD) between the model and the target structure. Maximum-likelihood MR functions, implemented in Phaser, improve the success rate by using more discriminating rotation and translation functions, which can incorporate partial structure information. The 'tree search with pruning' algorithm in Phaser iteratively links anisotropy correction, model generation, rotation function, translation function, packing function, and rigid-body refinement to solve complex asymmetric units. The article presents four case studies to illustrate how Phaser can be used effectively in standard automated MR mode and how modifications to the automated search strategy can be made for problematic cases, such as multiple copies of the same component or varying B-factors.