Electrochemical systems as such fuel cells or batteries could play an important rule in the increasing energy demand. They are based on red-ox reactions in which the reductant gets oxidized on the anode and the oxidant gets reduced on the cathode. In low temperature fuel cells (FCs), anode and cathode are generally separated by an electrolyte that works as ionic exchange membrane. The most used low temperature abiotic FCs work utilizing hydrogen (PEMFC) or methanol (DMFC) as anode fuel and oxygen at the cathode for completing the red ox reaction.Both reactions are possible and enhanced by the utilization of inorganic catalysts mainly based on platinum. FCs are not yet commercialized and this is mainly due to the tremendous cost of noble metals as anode/cathode catalyst that corresponds to almost the 50% of the overall cost of the FC. Consequently, new lines of research were opened trying to study new non-platinum group catalysts for reducing at least one order of magnitude the cost. Moreover, improvements on the materials have been also pursed and achieved in order to avoid electrode flooding, enhance materials durability and optimize the cost-efficiency of the FC. Also water demand and sanitation is an important problem that needs to be faced and possibile solutions need to be further investigated. Recently, microbial and enzymatic red ox reactions have been utilized with different important outputs. The new field of interest called bioelectrochemistry is able to utilize different redox reactions that are achieved by bacteria metabolism or enzymatic activity. The products of those reactions in bioelectrochemical systems (BESs) are various: i) positive electrical generation, ii) removal of organics and pollutants, iii) transformation of heavy metals, iv) water desalination, v) biosensors. Moreover, if external power is applied, hydrogen or other marketable compounds can be produced. Also in this case, several problems hinder the large scale commercialization. Several anologies and differences can be found between the abiotic and biotic (BES) fuel cells but only a critical analysis of materials and processes utilized can led to real advantages for biofuel cells. In this work, we sinthesize our experience in the past years to underline our discoveries and the future directions to follow. Starting from the anode, different species of electroactive bacteria are naturally able to oxidize and consequently degrade organic compounds and release electrons on the conductive electrode mainly carbonaceous-based. Those materials have been modified in order to increase bacteria attachment, faster the start up and led to higher current generated and organics degraded. Modifications were done introducing on the surface functional groups that facilitate electroactive bacteria to attach. Further studies should be directed on better understanding the rule of surface morphology on bacteria attachment. Moreover, the selection of different bacteria consortium directly attached on the electrode for enhancing electroactivity and current generation for long time experiments need to be investigated. Different cathodes instead have been investigated. Most of the cathode utilized were based on platinum but the cost is not sustainable for large scale applications. Other options are currently investigated with the utilization of: i) oxygen reducing enzymes, ii) biocathode, iii) non-PGM catalysts, iv) high surface area activated carbons. Enzymatic reduction of oxygen has the highest electrocatalytic activity at neutral conditions but the deactivation is very fast and consequently does not seem promising. Microbial catalysis has still to be fully understood but in few cases it has been proven the positive effect of bacteria grew carbonaceous towards reduction reaction. Non-PGM and activated carbon catalysts showed high electrocatalytic activity towards oxygen reduction reaction, high durability and high resistance to get poisoned in wastewaters. Any cathode utilized suffer dramatically from precipitation of carbonates species that clogs pores and decrease performances over time. Further investigations should led to combine microbial and inorganic catalysts for further improvements. The major problem related with lab scale BESs is the optimal working conditions that often are very different compare to the natural environments boosting up significantly the output. Bacteria activity in fact is increased by high temperature, presence of buffer that has ideal pH and large availability of easily degradable organics. At the contrary, in natural environment, temperature is lower than 30°C, the pH is not always neutral and organics are much more complex to degrade. As consequence of those above mentioned causes, the achievable performances are much lower. All those improvements achieved in BESs need to be further pursued in large scale and real environment. In our opinion, the main problem remain the lack of a common design that could boost power generation and allow an efficient water treatment.