Fisetin, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one, is a plant flavonoid initially isolated from Rhus cotinus L. This bioactive molecule often occurs in herbal teas and strawberry and has been extracted using aqueous methanol, water, and supercritical fluids. Besides keeping in view its pharmacological importance, microorganism such as yeast (Saccharomyces cerevisiae) and certain bacteria such as Escherichia coli have been successfully engineered for the enhanced production of fisetin from 4-coumaric acid and amino acids. The evaluation of available clinical records indicated that the oral administration of fisetin especially late in life (old age) can restore tissue homeostasis, inflammations, and certain type of cancers such as lung, bladder, breast, and blood cancer. Moreover, the administration of fisetin to wild-type mice late in life restored tissue homeostasis and control senescence-associated secretory phenotypes to extend the median and maximum lifespans.