Acetophenone is an important chemical intermediate often employed in the production chain of many pharmaceuticals, agrochemicals, food, and cosmetic products. It is industrially produced as a byproduct of the Hock process. However, a growing demand for acetophenone has necessitated consideration of alternative production routes. The oxidation of ethylbenzene to acetophenone (OEB-A) is one of the most considered alternatives due to the low cost and availability of ethylbenzene (EB). The EB is one of the products of refinery downstream processes that is obtained from the xylene/EB isomerization unit. Although the OEB-A reaction is considered inexpensive, it has not been of great interest due to the inert behavior of C−H bond, relatively low acetophenone selectivity, and cumbersome separation strategies for extracting acetophenone from other reaction byproducts. In this Review, we discuss the recent advances in the OEB-A reaction covering both homogeneous and heterogeneous systems. Advances in catalyst design and development including ligand design and coordination strategies and tuning of support properties have, over the years, proven to be effective in increasing acetophenone selectivity during the OEB-A process. Exploring a single-atom catalyst's definitive active centers and high atom efficiency in the OEB-A reaction has demonstrated high-throughput results, even though not well harnessed due to the challenges of controlled synthesis of single-atom metal catalyst. Solvent-free, the OEB-A reaction has demonstrated to be attractive due to its ease of product collection and environmental friendliness. Green synthesis strategies such as metal-free OEB-A reaction and CO 2 -assisted OEB-A reaction have been reviewed. The CO 2 assisted OEB-A reaction has not received the desired attention, even though considerable improvement in catalytic performance was reported. Considering the importance of carbon circular economy and the ready availability of CO 2 , the CO 2 assisted OEB-A reaction could be an interesting research focus in the near future.