In 1985, Fresnadillo moved to Madrid. He started out in photography and cinema studies and then began his career in short films. In 1987, he set up a production company, which produced several short films and commercials. Fresnadillo went on to become a production assistant for Gustavo Fuertes' short film El juicio final (The Final Judgment) (1991) In 2006, he directed 28 Weeks Later, the sequel to Danny Boyle's 2002 film 28 Days Later (released in 2007).