Most biologic processes exhibit significant deuterium isotope effects, which can measurably alter the abundances of stable hydrogen isotopes (1H and 2H) in biomolecules. A longstanding hope is that different organisms, reactions, or environments will result in characteristic 2H/1H ratios that we can learn to interpret. In this seminar I will summarize our efforts to understand the biochemical mechanisms that control H-isotopic fractionation in lipids, molecules that are well preserved in the sedimentary record and potentially offer insight into ancient metabolism and environments. In contrast to C and N isotopes, H-isotope signals arise from a combination of effects distributed across central metabolism, particularly those that conserve reducing power as NADPH. Both depletions and enrichments of 2H in the same environment are simultaneously possible, and provide a potential biosignature. We will conclude by considering the likelihood of such fingerprints being preserved in rocks from the early Earth, or in extraterrestrial materials.