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 PPARalpha transcription factor, is a "missing link" in the biology of fasting, inducing adipose tissue lipolysis, liver ketogenesis, and metabolic adaptation to the fasting state.