Despite the expanding literature describing techniques useful for growing crystals of proteins, successful crystallization remains a largely empirical, operator-dependent science. Detergents, such as beta -OG, have been found to be useful additives in the crystallization of both membrane and soluble proteins. We describe the use of detergents to optimize crystallization of four soluble proteins, which resulted in improved crystal quality and reproducibility of results, including promoting the growth of single crystals as opposed to polycrystals and cluster crystals, enhancing the crystal's X-ray diffraction characteristics, and improving the reproducibility of crystal growth.