Fuel cells are electrochemical membrane reactors that are able to convert chemically stored energy directly to electrical energy at high thermodynamic efficiencies. The present paper summarizes the current status and the future needs in fuel cell science and engineering. In the first part, possible primary fuels, alternative fuel processing pathways, and conceptual design aspects of fuel cell systems are discussed. In the second part, important trends in the development of functional materials for the preparation of stable high-performance fuel cells with extended longevity are presented. Thereby, different types of fuel cells are discussed, namely, enzymatic fuel cells (EFCs), alkaline fuel cells (AFCs), polymer electrolyte fuel cells (PEFCs), direct methanol fuel cells (DMFCs), direct ethanol fuel cells (DEFCs), phosphoric acid fuel cells (PAFCs), molten carbonate fuel cells (MCFCs), and solid oxide fuel cells (SOFCs).