Extremophiles, notably archaea and bacteria, offer a good platform for treating industrial waste streams that were previously perceived as hostile to the model organisms in microbial electrochemical systems (MESs). Here we present a critical overview of the fundamental and applied biology aspects of halophiles and thermophiles in MESs. The current study suggests that extremophiles enable the MES operations under a seemingly harsh conditions imposed by the physical (pressure, radiation, and temperature) and geochemical extremes (oxygen levels, pH, and salinity). We highlight a need to identify the underpinning mechanisms that define the exceptional electrocatalytic performance of extremophiles in MESs.