Addressing major environmental issues, such as water pollution, is essential nowadays in realizing sustainable development. The ever-increasing world population and industrial development have led to the introduction of diferent types of chemicals to the environment, leading to considerable deterioration in environmental quality. A major class of these chemicals is phenolic compounds, which are hazardous pollutants and highly toxic even at low concentrations. In recent years, researchers have realized the importance of extracting new bacterial strains that are efective in treating diferent types of highly contaminated wastewaters at diferent severe conditions. They also focused considerable amount of research on developing new types of reactors that would provide eicient mixing and reduce mass transfer limitations. The aim is to develop and evaluate efective reactor systems and biocatalysts for the biodegradation of major contaminants in petroleum reinery wastewater. This chapter examines the diferent available options for the treatment of reinery wastewater with more focus on novel biotreatment options.