A sufficient energy supply is essential for life; consequently, multiple mechanisms have evolved to ensure both energy availability and conservation during fasting and starvation. Two reports in this issue of Cell Metabolism (Badman et al., 2007, Inagaki et al., 2007) demonstrate that FGF21, a circulating protein produced in the liver in response to the PPARα transcription factor, is a “missing link” in the biology of fasting, inducing adipose tissue lipolysis, liver ketogenesis, and metabolic adaptation to the fasting state.