Conspectus Low-temperatureion-exchange membrane hydrogen fuel cells, as zero-emissionpower sources, can largely preserve the merits of gasoline engines,including rapid fueling, extended cruising range, and low maintenancecost. To enable the widespread prevalence of fuel-cell automobiles,the U.S. Department of Energy (DOE) has set a long-term fuel-cellsystem cost target of US$30 kW(-1). Over past decades,proton-exchange membrane fuel cell (PEMFC) technology has developedrapidly, resulting in the first commercial sales of fuel-cell-poweredvehicles. Although there has been great success, the mass market penetrationof PEMFCs is currently hindered by the excessive reliance on expensiveplatinum group metal (PGM) catalysts. Anion-exchange membrane fuelcells (AEMFCs), because of the alkaline environment that permits theuse of PGM-free catalysts, have become an alternative technology withinherent long-term cost advantages. Thus far, significant progresshas been made in the exploration of PGM-free catalysts for the oxygenreduction reaction at the AEMFC cathode, some of which have shownintrinsic catalytic properties comparable to PGM catalysts. However,the development of PGM-free catalysts for the anodic hydrogen oxidationreaction (HOR) has lagged behind, presumably owing to its sluggishkinetics in alkali. In alkaline media, the HOR kinetics is about 2orders of magnitude slower than that in acid, which demands higherPGM loadings to reach similar fuel-cell performance in PEMFCs. SinceRaney nickel (Ni) was explored for alkaline HOR catalysis in 1960s,research on Ni-based HOR catalysts has begun and now is flourishing,primarily thanks to their favorable adsorption energies of key HORintermediates (e.g., Ni-H-ad and Ni-OHad). At present, a number of strategies have been developedto improve HOR performances of Ni-based materials, such as alloying,Ni nitridation, and alloy amorphization, which yield cost-effectiveHOR catalysts that rival or even exceed the activity and stabilityof PGM counterparts. In this Account, we describe our recentresearch endeavors towardthe development of efficient Ni-based HOR catalysts for practicalAEMFC anodes. First, we briefly highlight the important merits ofAEMFC technology and why Ni-based materials are appealing for alkalineHOR catalysis. Critical innovations in the design of Ni-based nanostructuredand bulky catalysts were then discussed, showing their great promiseto catalyze alkaline HOR that traditionally relied on PGMs. To demonstrateutility, performances of the elaborately designed Ni-based catalystsunder realistic fuel-cell conditions were examined, along with aninitial effort to develop a CO-tolerant AEMFC anode. We conclude byoutlining future research directions that allow access to next-generationPGM-free HOR catalysts for advanced AEMFCs.