Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfil a range of ecological roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related parameters, including those related to cardiovascular and brain function. Over recent years the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and towards their modulation of cellular signal transduction pathways. To date little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. This review therefore summarises the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecological roles and potential endogenous signalling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of ‘cross-kingdom’ signalling predicated on the many conserved similarities in plant and human cellular signal transduction pathways.