Investigation into DNA from archeological remains offers an inestimable tool for unraveling the history of humankind. However, a series of basic and technical difficulties renders the analysis of ancient DNA (aDNA) molecules troublesome, depending either on their own peculiar characteristics or on the complexity of processes affecting the bone matrix over time, all compromising the preservation of ancient DNA. This review underlines the contribution of many different disciplines, in particular molecular biology and genetics, to overcome these obstacles. The role of each expertise is illustrated to appropriately address the questions arising in aDNA investigations. © 2004 Wiley-Liss, Inc.