Small organic molecules play a major role towards affordable, orally consumable and nontoxic drug discovery. These small molecules have essentially driven the healthcare for the vast majority of the human population eversince, aspirin was synthesized in 1899 by Bayer. A few famous small molecule drugs include ibuprofen, retrovir, xarelto, cyclophosphamide, lipitor and vitrakvi. The efficacy of these drugs are highly sensitive towards the solubility of the active pharmaceutical ingredients (APIs) under physiological conditions. To increase the solubility in the water-rich cellular environments, hydrogen-bonded motifs with -OH, -COOH, -RNH, -CONH2 groups are routinely utilized. The role of hydrogen-bonding in bestowing stability, flexibility and diversity in crystalline packing has been richly studied. Subtle changes in RO-H…O angles and dihedral angles have been shown to stabilize a particular polymorph over other possible structures. The correspondence between the structure of molecules and their eventual state of aggregation in the solid-state has significantly been advanced through crystal engineering. The concept of supramolecular synthon as proposed by Desiraju has been a crucial design strategy in molecular crystals. Crystal engineering has led to advancements in flexible crystals with advanced optical properties and electron/hole or spin-transport materials. In the context of the aggregates of organic acids and bases, the eventual fate within the crystal can either be a co-crystal stabilized by hydrogen-bonded network of (formally) neutral molecules or a salt formed by a proton transfer from the protic acid to the base. The salts are stabilized by Coulombic forces or the Madelung energy between the oppositely charged ionic entities in the lattice. The dynamical aspects involved with the proton migration from the acid to base leading to a cross-over from a formally co-crystal state to a salt state has been studied in details. The X-H bond-dissociation energy depends critically both on the polarity of medium and the state of aggregation.