The expression 'crystal clear' stems from the science of crystallography, which determines the detailed atomic structures of materials by exposing crystals to X-rays. Protein structures are pivotal to the success of rational drug design and other biotechnology applications; however, obtaining high quality crystals poses a major problem to progress. Nucleation is the first step that determines the entire crystallization process, thus control of crystal nucleation would tackle the problem at its conception. A search for a 'universal' nucleant, a substance that can induce nucleation of any protein, is therefore on-going. We report the advances that have been made in this area, highlighting the success of especially engineered as well as naturally structured surfaces.