Persulfate is the newest oxidant that is being used for in situ chemical oxidation (ISCO) in the remediation of soil and groundwater. In this review, the fundamental reactions and governing factors of persulfate relevant to ISCO are discussed. The latest experiences for ISCO with persulfate are presented, with a focus on the different activation methods, the amenable contaminants, and the reactions of persulfate with porous media, based primarily on a critical review of the peer-reviewed scientific literature and to a lesser extent on non-reviewed professional journals and conference proceedings. The last sections are devoted to identifying the best practices based on current experience and suggesting the direction of future research.