In 1977, Nespoli entered the Military Parachuting School of Pisa, where he obtained the qualification of non-commissioned parachuting instructor. In 1980, he joined the Italian special forces, obtaining the qualification of paratrooper raider. He was sent to Lebanon in the Multinational Peace Force, from 1982 to 1984; with the rank of major, he is a reserve officer in the Italian Army. He obtained a Bachelor of Science in Aerospace Engineering in New York in 1988 and a Master of Science in Aeronautics and Astronautics in 1989 at the Polytechnic University of New York. In 1990, he graduated in Mechanical Engineering at the University of Florence. He started working for ESA in 1991 and left for his first mission in 2007. In total, in the three missions of 2007, 2010 and 2017, Nespoli remained in space for 313 days, 2 hours and 36 minutes. Following the retirement from his astronaut career, he has been teaching Human Spaceflight and Operations at Politecnico di Milano in the Space Engineering course since 2023.