Microbial fuel cells (MFC) are the archetype microbial bioelectrochemical system (BES), producing electricity from microbially catalyzed anodic oxidation processes. The greatest potential of MFC lies in the use of wastewater as a substrate (fuel), which allows combining waste treatment and energy recovery. Recently, a development has been initiated that expands the scope of these bioelectrochemical systems from power generation to an increasing number of further applications. This development has become possible by the introduction of new cathode catalyst concepts. The corresponding devices, here summarized as MXCs-the X standing for the different types and applications-share one common element: the microbial anode. The cathode, however, has to fulfil rather different tasks and thus differs quite remarkably across these systems. In this critical review we analyze the different cathode tasks and the resulting requirements for the respective cathode and discuss the available catalyst options in the light of their major advantages and weaknesses. These catalyst options comprise inorganic, biomolecular as well microbial catalyst systems. Hereby, special emphasis is put on a comparative analysis of chemical and biological cathodes and their individual potentials and limitations. For this purpose, criteria are defined based on relevant properties (performance, price, longevity, etc.) and are evaluated by means of a multi-factor analysis, based on the individual target reaction and catalyst. This analysis is exemplarily elaborated for the oxygen reduction reaction (typical for MFCs) and for the hydrogen production (in MECs) (91 references).