MELISSA (Micro Ecological Life Support System Alternative) is a research project for the development of advanced life support systems, conducted by the European Space Agency. Its basic design is based on a loop of bioreactors with the main objective of the regeneration of the wastes generated by a crew into an edible material, with concomitant regeneration of the atmosphere for human respiration. The MELISSA Pilot Plant is a European facility to study and validate advanced life support systems. It has as main objectives the ground demonstration and characterization of a closed loop concept. This includes the development of the associated technology for its successful continuous operation such as water treatment, pathogen detection, food preparation, and other related items. At present time, the main research project developed in the Pilot plant is the MELISSA project. A key point in its development is the collection of experimental data under real operating conditions in order to perform mathematical modeling. This is a key issue in the approximation followed, both for the control and simulation of the individual bioreactors and the complete loop. The state of the art of the pilot plant is discussed, and particular emphasis is made in the description of the continuous operation of the interconnected bioreactors. Also the necessary associated research, required for its successful operation, such as the development of an advanced control system or the analysis of the effect of the malfunction of one compartment, on the subsequent ones are reviewed.