Site isolation and phase cooperation are two important concepts in selective oxidation catalysis and are useful in the design and discovery of new catalysts. Site isolation deals with the limitation of active oxygens at the catalytic site with the aim to maximize the formation of desired selective oxygenated products and to minimize overoxidation to waste products(COx) [1]. Phase cooperation deals with the concept that two properly chosen phases of complimentary catalytic properties, when brought into intimate (nanoscale) contact with each other, can be made to cooperate synergistically with each other to give higher yields of desired selective oxidation products than what can be obtained by either of the two phases operating separately and independently from each other [2]. This cooperation of phases is of particular importance when all of the key catalytic functionalities cannot be incorporated into a single phase. These two principles, were first proposed and articulated by SOHIO researchers in the late 1950s and served as useful guidelines for the invention and development of selective oxidation and ammoxidation catalysts, many of which were ultimately successfully commercialized. After all these years, these concepts are still very much applicable to explain the behavior of many catalysts and remain a useful tool for the design of new catalysts in the area of selective oxidation and ammoxidation catalysis of light hydrocarbons and related fields. A retrospective and update of the site isolation and phase cooperation concepts is presented here, and includes their application to new and challenging catalytic problems facing the scientific and technological world. (C) 2014 Published by Elsevier B.V.