This chapter deals with an analysis of the history, current status of technology,potential applications and techno-economic challenges ofDMFCs. The basic aspects of DMFC operation are presented with particular regard to thermodynamics, performance, efficiency and energy density characteristics. The historical development of DMFC devices and components is analyzed with special regard to the study of catalysts and electrolytes. The section on fundamentals is focused on the electrocatalysis of the methanol oxidation reaction (MOR) and oxygen electroreduction. The current knowledge in the basic research areas is presented and particular emphasis is given to required breakthroughs. The technology section deals with the fabrication methodologies for the manufacturing of membrane electrode assemblies membrane electrode assembly (MEA), stack hardware and system design. Recent efforts in developing DMFC stack for both portable and electro-traction applications are reported.