Functional genomics allows for the activity of the whole genome to be surveyed at once. Using this technology for the identification of novel targets and their validation in disease-specific contexts has profound implications for the future of drug discovery. Now researchers have the technological means to gather comprehensive data on basic biological phenomena and disease mechanisms, while monitoring the effect of drug candidates on a molecular level. Pathway analysis can facilitate the genetic profiling of patients and, in turn, predict individual responses to treatment regimes. Functional interrogation of a disease-specific phenotype at a whole genome level (through, for example, the use of whole genome RNAi libraries) allows for the identification of critical regulators in complex biological systems, and the detection of putative targets for future therapeutic intervention. The authors describe the applications of functional genomics in models of breast cancer and the integration of these disparate technologies, specifically in the context of the search for novel therapeutic targets.