Activated sludge has been widely adopted as the cornerstone of conventional sewage treatment for over 50 years. This process can reduce biochemical oxygen demand (BOD) in wastewater and protect public health, with many systems able to remove nutrients as well. While activated sludge continues to satisfy many treatment targets, the demands on wastewater treatment are changing. There are concerns that toxic and difficult-to-degrade contaminants are contributing to environmental and human health issues. There is also increasing interest in potable reuse to strengthen water resiliency and the waste-to-resource paradigm; however, when biological secondary treatment is used, additional treatment is needed for reuse. Chemical oxidation may be an effective alternative to activated sludge to destroy difficult-to-degrade contaminants. Compared to biological systems, chemical oxidation may also be easier to operate and maintain, requiring less space for more effective treatment. This article presents a critical review of current activated sludge-based sewage treatment practices and explores the opportunity to replace biological secondary wastewater treatment with chemical oxidation. Some opportunities include the ability of chemical oxidation to degrade contaminants of emerging concern (CECs); rapid start up and shut down; and avoidance of issues associated with biological treatment such as toxic loadings, biomass washout, difficulties settling sludge, and sludge handling and disposal. This review focuses on chemical oxidation as an alternative to biological secondary treatment for municipal wastewater. Most works included in this review are referenced in Google Scholar and the Web of Science, with the majority being published between 2000 and 2023. Trends revealed include a substantial increase in investigations regarding biological treatment, but much less literature focused on chemical oxidation of municipal secondary wastewater. There were reports covering chemical oxidation for industrial wastewater and for tertiary treatment of municipal wastewater, but not for chemical oxidation as a secondary treatment method for municipal wastewater."