Plant phytochemicals achieve hormesis through multifocal pathway inhibition. Our health strongly benefits from interactions of a large number of plant molecules in our diet with key regulators of mammalian physiology (adapted from ). Various plant-derived molecules are synthesized as secondary metabolites in response to stress. During adversity in the context of particular environmental stresses, animals have retained the ability to sense these stress signaling molecules synthesized by their distant ancestors, through enzymes and receptors which regulate inflammation-energy-metabolism pathways to protect and to increase the survival of the organism. Abbreviations used: PKC, protein kinase C; PKD, protein kinase D, IKK2, inhibitor of IkB kinase 2; ROS/RNS, reactive oxygen/nitrogen species; NR, nuclear receptor; AMPK, AMP-activated protein kinase; TSC, tuberous sclerosis complex mTOR, mammalian target of rapamycin; R6SK ribosomal S6 kinase; PI3K, phosphoinositide 3-kinase; PDK, pyruvate dehydrogenase kinase; AKT/PKB, protein kinase B; PGC1, peroxisome proliferator-activated receptor c coactivator 1; SIRT, sirtuin; FOXO, forkhead box O.