Due to the toxicity of bioaccumulative organohalides to human beings and ecosystems, a variety of biotic and abiotic remediation methods have been developed to remove organohalides from contaminated environments. Bioremediation employing organohalide-respiring bacteria (OHRB)-mediated microbial reductive dehalogenation (Bio-RD) represents a cost-effective and environmentally friendly approach to attenuate highly-halogenated organohalides, specifically organohalides in soil, sediment and other anoxic environments. Nonetheless, many factors severely restrict the implications of OHRB-based bioremediation, including incomplete dehalogenation, low abundance of OHRB and consequent low dechlorination activity. Recently, the development of in situ chemical oxidation (ISCO) based on sulfate radicals (SO
4
·−
) via the persulfate activation and oxidation (PAO) process has attracted tremendous research interest for the remediation of lowly-halogenated organohalides due to its following advantages, e.g., complete attenuation, high reactivity and no selectivity to organohalides. Therefore, integration of OHRB-mediated Bio-RD and subsequent PAO (Bio-RD-PAO) may provide a promising solution to the remediation of organohalides. In this review, we first provide an overview of current progress in Bio-RD and PAO and compare their limitations and advantages. We then critically discuss the integration of Bio-RD and PAO (Bio-RD-PAO) for complete attenuation of organohalides and its prospects for future remediation applications. Overall, Bio-RD-PAO opens up opportunities for complete attenuation and consequent effective in situ remediation of persistent organohalide pollution.