Abstract: Almost all bacteria synthesize two types of toxins—one for its survival by regulating different cellular processes and another as a strategy to interact with host cells for pathogenesis. Usually, “bacterial toxins” are contemplated as virulence factors that harm the host organism. However, toxins produced by bacteria, as a survival strategy against the host, also hamper its cellular processes. To overcome this, the bacteria have evolved with the production of a molecule, referred to as antitoxin, to negate the deleterious effect of the toxin against itself. The toxin and antitoxins are encoded by a two-component toxin-antitoxin (TA) system. The antitoxin, a protein or RNA, sequesters the toxins of the TA system for neutralization within the bacterial cell. In this review, we have described different TA systems of bacteria and their potential medical and biotechnological applications. It is of interest to note that while bacterial toxin-antitoxin systems have been well studied, the TA system in unicellular eukaryotes, though predicted by the investigators, have never been paid the desired attention. In the present review, we have also touched upon the TA system of eukaryotes identified to date. Key points: Bacterial toxins harm the host and also affect the bacterial cellular processes.The antitoxin produced by bacteria protect it from the toxin’s harmful effects.The toxin-antitoxin systems can be targeted for various medical applications. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.