The challenge in supporting biological macromolecule crystallization projects for structure based drug design is to develop robust crystallization systems, from which high-resolution crystal structures for a variety of ligand complexes can be obtained. Each biological macromolecule is unique, often requiring the testing of binding partners, additives, purification tag placement and crystallization methods, in addition to solution condition screening. It is often a combination of a number of these factors that lead to the most robust crystallization system. In this presentation we will discuss case studies illustrating how the use of additives such as ionic liquids, second site binders, crystallization method, tag placement and purification methods have provided high quality crystals for a number of biological macromolecules.