The mechanistic basis of the immune response in Drosophila has been widely studied; however, little is known about the evolutionary and physiological mechanisms that drive local adaptation to pathogens. It is also unknown if this adaptation is dependent on factors such as the infected life-stage, route of infection or pathogen type(s) and the associated trade-offs. We have used Drosophila outbred populations, in collaboration with Sara Magalhães (University of Lisbon) and Luis Teixeira (IGC), to conduct experimental evolution to different and contrasting immune challenges. We have shown that adaptation to pathogens often relies on simple genetic basis, is highly pathogen specific, highly contingent on infection route and implies little trade-offs with other life-history traits. We are currently determining in detail the genetic changes that underlie these adaptive processes using deep-sequencing technology in collaboration with Christian Schlötterer (Vienna, Austria).