The 2012 Nobel Prize in Chemistry was awarded to two American Scientists, Dr. Robert Lefkowitz and Brian Kobilka, for their fundamental contributions in the discovery and mechanism of G protein coupled receptors (GPCR). GPCR not only constitute one of the most important modular systems for cellular signaling; but also more than half of the prescription-drug targets. Through the development of many new techniques, and focused investigation on the receptor of “fight or flight hormone”, the adrenergic receptor, Prof. Lefkowitz led the GPCR research since 1970s. Lefkowitz’s contributions to our understanding of GPCR include but not limited to the identification of GPCR by radio-ligand binding, construction of the ternary complex model, elucidation of the receptor desensitization mechanism, and the concept of the receptor biased signaling. Professor Lefkowitz and Dr. Kobilka cloned the first GPCR gene for a diffusive ligand, which led to the identification the GPCR superfamily. In setting up his independent lab, Kobilka broke the technical barrier for crystalizing GPCR with diffusive ligands, and solved the first GPCR/G protein complex structure. Therefore, our current understanding of GPCR has greatly benefitted from the work of Profs. Lefkowitz and Kobilka. With the current great progresses in GPCR working mechanism and development of important techniques, we are now poised to make even greater discoveries in the future, including the characterization of orphan GPCR functions, complex structures of GPCR with their effectors including arrestin, and most importantly, identification of new pharmacological agents based on new structural information. These discoveries will not only help in detailing mechanisms of biological signal transductions, but will also bring great innovations to clinical treatment for many devastating diseases.