The interactions involving the side chains of weakly polar aromatic amino acid residues, e.g., Phenylalanine (Phe), Tyrosine (Tyr) and Tryptophan (Trp) generally reside at the interior of proteins and help in the stabilization of globular protein structures. The aromatic electron cloud of the aromatic rings of these amino acids are delocalized on both sides of the planer rings, so that there is a small partial negative charge on the face and a small partial positive charge on the hydrogen atoms of the edge, which leads to the possibility of electrostatic interactions. These interaction play a vital role nanofiber based vaccine adjuvants, and cocaine vaccine development and increasing interest and structure-based drug development. Apart from electrostatic forces, aromatic interactions also consist of van der Waals and hydrophobic forces. These weakly polar interactions are enthalpically comparable to a hydrogen bond. Protein engineering methods have revealed that introducing aromatic pairs and aromatic clusters increases the thermal stability of proteins and it has been demonstrated that the introduction of an additional aromatic interaction improved the thermophilicity and thermostability of the family of 11 xylanase. These weakly polar interactions also have a significant role in the stability of DNA. Different types of weakly polar interactions involving the aromatic side chains are discussed below.