Bacterial toxin-antitoxin (TA) systems are formed by a stable toxin and its cognate labile antitoxin, and exist almost in all bacteria. Recently, the chromosome-encoded II-type TA systems have been demonstrated to function as stress-response elements and help bacteria acclimate to different environmental stresses through the action of toxins to various cellular targets. Therefore, the modulation of toxin activities is crucial to II-type TA systems triggering bacterial response to environmental stresses. In this review, we describe the regulation mechanisms of II-type TA system activity, and briefly introduce our recent studies on the regulation of the II-type TA systems in the model cyanobacterium Synecocystis sp. PCC6803.