New developments in evolutionary biology and molecular genetics have far-reaching consequences for physiological science since they imply major extensions or even replacement of the Modern Synthesis (Neo-Darwinism) [1, 2, 3, 4, 5]. The Modern Synthesis was a mid-twentieth century gene-centric view of evolution, based on random mutations accumulating to produce gradual change through natural selection. Any role of physiological function in influencing genetic inheritance was excluded. The organism became a mere carrier of the real objects of selection: its genes. We now know that genetic change is far from random and often not gradual. Molecular genetics and genome sequencing have deconstructed this unnecessarily restrictive view of evolution in a way that reintroduces physiological function and interactions with the environment as factors influencing the speed and nature of inherited change. Acquired characteristics can be inherited, and in a few but growing number of cases that inheritance has now been shown to be robust for many generations. The twenty-first century can look forward to a new synthesis that will reintegrate physiology with evolutionary biology. This lecture will outline the key features of the new synthesis and why it could bring physiology back onto centre stage in biology. “It is hard to think of a more fundamental change for physiology, and for the conceptual foundations of biology in general.” [1]