Our laboratory has had a long-standing interest for interactions between viruses and their hosts. This led us in the past to study the biology of pathogens such as human immunodeficiency virus and hepatitis B virus, and to develop virus-based delivery systems for human gene therapy. Over the last ten years, our research has shifted towards the field of epigenetics, to explore the impact of retroelements and their controlling mechanisms on the development and physiology of higher organisms, including humans. Of particular interest to us is the so-called KRAB’n’KAP system, which comprises some 400 KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1, and evolved from a line of defense against retroelements to a true master regulator of mammalian physiology.