Protein crystallography emerged in the early 1970s and is, to this day, one of the most powerful techniques for the analysis of enzyme mechanisms and macromolecular interactions at the atomic level. It is also an extremely powerful tool for drug design. This field has evolved together with developments in computer science and molecular biology, allowing faster three-dimensional structure determination of complex biological assemblies. In recent times, structural genomics initiatives have pushed the development of methods to further speed up this process. The algorithms initially defined in the last decade for structure determination are now more and more elaborate, but the computational tools have evolved toward simpler and more user-friendly packages and web interfaces. We present here a modest overview of the popular software packages that have been developed for solving protein structures, and give a few guidelines and examples for structure determination using the two most popular methods, molecular replacement and multiple anomalous dispersion.