In this paper, the design of fuel cells for the main energy supply of passenger transportation aircraft is discussed. Using a physical model of a fuel cell, general design considerations are derived. Considering different possible design objectives, the trade-off between power density and efficiency is discussed. A universal cost–benefit curve is derived to aid the design process. A weight factor w P is introduced, which allows incorporating technical (e.g., system mass and efficiency) as well as non-technical design objectives (e.g., operating cost, emission goals, social acceptance or technology affinity, political factors). The optimal fuel cell design is not determined by the characteristics of the fuel cell alone, but also by the characteristics of the other system components. The fuel cell needs to be designed in the context of the whole energy system. This is demonstrated by combining the fuel cell model with simple and detailed design models of a liquid hydrogen tank. The presented methodology and models allows assessing the potential of fuel cell systems for mass reduction of future passenger aircraft.