Site-specific DNA recombinases (SSRs) are very versatile genetic tools which have found widespread application in modern molecular biology. Although mostly prokaryotic in origin, these enzymes catalyse a wide variety of reactions, like DNA deletions, inversions, translocations or insertions also in the eukaryotic system. This versatility made one of the members of this family of enzymes, the Cre recombinase from phage P1 the tool of choice for gene rearrangements in mouse transgenics. Several other recombinases, including the yeast Flp or the C31 integrase from the Streptomyces phage, followed thereafter and offered a plethora of new options especially when combined with other SSRs. With ongoing sequencing projects, the list of available recombinases to choose from may grow tremendously in the near future. Combined with approaches such as in vitro evolution, this development could provide researchers with countless tailor-made tools which would even allow speculating about therapeutic applications. This review aims at giving an introduction to site-specific recombination as exemplified by the Cre recombinase. Recent progress in the field will be outlined (e.g. cassette exchange technologies, large chromosomal rearrangements, SSRs as cloning devices) and its potential for future applications in basic and clinical research will be discussed. Furthermore, promising novel SSR candidates for genome engineering, which have not been applied extensively so far, will be presented.