This study shows that exposure to low concentrations of the polyphenol tannic acid (TA) induces potent life-prolonging properties in Caenorhabditis elegans. In addition, enhanced thermal stress resistance, reduced growth, and slightly increased oxidative stress resistance were observed, although reproductive capacities and pharyngeal pumping rate were not modulated. Exploiting a suite of 14 mutant strains revealed that the mitogen-activated protein kinase kinase SEK-1 (SAPK/ERK kinase) is a key player involved in TA-mediated longevity. It is conceivable that TA mimics pathogen action and therefore activates the SEK-1-mediated pathogen resistance pathway. This pathway is thought to inhibit potential detrimental effects of TA and may also be involved in the longevity process. The observed dose response suggests the presence of a hormesis effect, and the growth impairment is in agreement with the "Disposable Soma Theory." This report underlines the uniqueness of TA-mediated longevity and facilitates a first glimpse into its complex mode of action.