Human factors are the principal cause of aircraft accidents, at a rate of 70 – 80%. Of these accidents, 10% are due to “disease” and the rest are due to “human error”. “Pilot incapacitation” is the term used in the literature to describe the inability of a pilot, who is part of the operating crew, to carry out his flight duties, because of one or more factors which arise in flight and affect either human physiology (i.e. disease, hypoxia) or human performance (i.e. fatigue). The incapacitation can be physical or mental, acute or progressive, evident or latent. It is evident that acute and latent incapacitation is the most dangerous for the flight safety. The COCKPIT project aims to the “in flight” monitoring -in a flight simulator environment- of a set of human physiology parameters (heart rate, breath rate, hemoglobin oxygen saturation, muscle tone and sleepiness), by using specialized sensors and advanced signal and image processing techniques. In particular, COCKPIT’s goal is to develop: (i) a real time “Cockpit Crew Health Monitoring System” and (ii) an “Early Warning System for the Second Pilot” so he resumes the control of the aircraft, thus minimizing the probability that an aircraft accident happens.