The research presented herein focus upon crystal engineering of co-crystals with an emphasis upon the exploration of co-crystals in the context of delineation of the reliability of hydrogen bonded supramolecular synthons and their hierarchies. The approach involves a combination of systematic Cambridge Structural Database analysis and a series of model co-crystal experiments. In addition, the viability of solid state methodologies toward supramolecular synthesis of co-crystals and the effect on polymorphism is also addressed. The application of the acquired knowledge is towards the crystal engineering of pharmaceutical co-crystals. The rational design and synthesis of pharmaceutical co-crystals accomplished by the selection of appropriate co-crystal formers facilitated by analysis of existing crystals structures in the CSD will be demonstrated. The processing of pharmaceutical co-crystals will also be addressed in terms of slurry conversion, solvent drop grinding and solution crystallization.