ABSTRACT The large serine recombinases (LSRs) are a family of enzymes, encoded in temperate phage genomes or on mobile elements, that precisely cut and recombine DNA in a highly controllable and predictable way. In phage integration, the LSRs act at specific sites, the attP site in the phage and the attB site in the host chromosome, where cleavage and strand exchange leads to the integrated prophage flanked by the recombinant sites attL and attR . The prophage can excise by recombination between attL and attR but this requires a phage-encoded accessory protein, the recombination directionality factor (RDF). Although the LSRs can bind specifically to all the recombination sites, only specific integrase-bound sites can pair in a synaptic complex prior to strand exchange. Recent structural information has led to a breakthrough in our understanding of the mechanism of the LSRs, notably how the LSRs bind to their substrates and how LSRs display this site-selectivity. We also understand that the RDFs exercise control over the LSRs by protein–protein interactions. Other recent work with the LSRs have contributed to our understanding of how all serine recombinases undergo strand exchange subunit rotation, facilitated by surfaces that resemble a molecular bearing.