The toxin-antitoxin (TA) system consists of a pair of co-expressed genes. The upstream gene encodes an unstable antitoxin protein, and the downstream gene encodes a stable toxin. The toxin-antitoxin system was originally found on the low-copy plasmid to maintenance the plasmid stability. Recently the TA loci have been widely identified on the chromosomes of bacteria, including the some pathogens. The TA systems play an important role in the bacterial growth control or the bacterial programmed cell death under starvation and other stress conditions. The toxin in different TA system has different cellular targets. CcdB toxin in the ccdAB system interacts with the catalytic GyrA subunit of gyrase to inhibit the DNA replication. RelE toxin in the relBE system assists the RNA cleavage at the ribosome A site with a high coden specificity. PemK toxin in the pemIK system and MazF toxin in the mazEF system are identified as endoribonucleases, which cleave the cellular mRNA in a sequence-specific manner to interfere with mRNA function and inhibit the protein synthesis. This review summarizes the mechanism of the toxin in TA system and evaluates the applications of TA system in the future.