Discontinuities in double-stranded DNA, such as DNA double-strand breaks (DSBs), pose a threat to genome stability. Homologous recombination is a process that not only effectively repairs DSBs, but also promotes preservation of genome integrity by repairing DNA discontinuities arising during DNA replication. Genetic analyses identified many genes involved in DSB repair and placed them in different pathways. Biochemical analyses have aided in placing the protein products in a mechanistic framework for the pathways, while molecular biological approaches, such as chromatin immuno-precipitation, have allowed the monitoring of protein composition near DSBs in populations of fixed cells. Progress in cell biological techniques has now made it possible to analyze proteins in their physiological environment of the living cell. Here, we describe how homologous recombination proteins have been characterized using the methods of cell biology. The current challenge is to integrate insights gained on the spatio-temporal behavior of DSB repair proteins using chromatin immuno-precipitation and live cell imaging in the established genetic and biochemical frameworks for mechanisms of DSB repair.