Advanced fuels for nuclear fusion — of which deuterium and 3He mixture is the leading candidate — could reduce tritium inventory, neutron fluence, structural damage, and activation in future reactors as well as allow for direct energy conversion. The feasibility of D-3He fusion is assessed based on recent developments in the areas of fuel resources, fusion and plasma physics, magnetic and inertial reactors, space propulsion, reactor safety, and waste disposal. It appears that D-3He fusion is not well suited to the conventional tokamak design (β ∼ 10%) because of excessive synchrotron loss and closed field topology. High-beta and/or non-Maxwellian plasma configurations are promising but at present lack a sufficient experimental database to predict reactor-relevant behavior. Space propulsion appears to be a most advantageous application of D-3He fusion.