The universal microbial cometabolism provides us with an effective approach to remove man-made xenobiotics. However, the cometabolic bioremediation of toxic organic compounds has not been widely initiated due to the obscure underlying fundamentals in the studies or applications of microbial cometabolism. This review summarizes the current research trends in mechanistic understanding of microbial cometabolism, especially with regard to its potential applications. The crucial factors including key enzyme, enzyme inhibition, toxic effects and energy regulation are discussed, which all significantly contribute to the cometabolic bioremediation of pollutants. The presented review of chlorinated ethylene cometabolism in this overview has further confirmed the fundamentals and hypotheses mentioned above, and thus cometabolism of chlorinated ethylenes has been regarded as a role model of pollution remediation technology using microbial cometabolism. The subsequent prospective research should provide insights into the ambiguous mechanism of microbial cometabolism and help us to develop more efficient bioremediation of progressive pollution.