Pharmaceutical cocrystals are crystalline molecular complexes containing therapeutic molecules. They represent an emerging class of pharmaceutical materials offering the prospect of optimized physical properties. This article highlights important opportunities and challenges associated with the design and synthesis of pharmaceutical cocrystals. Cocrystallization is first placed into context with the more established approaches to physical property optimization of polymorph, hydrate, and salt selection. A directed, intermolecular-interaction-based approach to cocrystal design is described. The enhancement of specific physical properties, such as dissolution rate and physical stability, is illustrated by summarizing several recent reports. Synthetic approaches to cocrystallization are considered; in particular, the selectivity and screening-related opportunities afforded by solid-state grinding and solvent-drop grinding methods are discussed. Finally, an outlook on future developments summarizes the growth potential in this field, especially with regard to targeted, informatics-driven cocrystal screening approaches.