Homologous recombination is crucial for genome stability and for genetic 
exchange. Although our knowledge of the principle steps in recombination and its 
machinery is well advanced, homology search, the critical step of exploring the 
genome for homologous sequences to enable recombination, has remained mostly 
enigmatic. However, recent methodological advances have provided considerable 
new insights into this fundamental step in recombination that can be integrated 
into a mechanistic model. These advances emphasize the importance of genomic 
proximity and nuclear organization for homology search and the critical role of 
homology search mediators in this process. They also aid our understanding of 
how homology search might lead to unwanted and potentially disease-promoting 
recombination events.