Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, this disease remains incurable. It is therefore important to develop additional novel therapeutic strategies and agents. Increased understanding of the biology and the molecular alterations present in breast cancer is facilitating the design of targeted therapies directed to oncogenic proteins. Here, we review the signaling pathways and proteins that participate in breast cancer proliferation and survival, with special emphasis in those that are druggable. We will also comment on how the knowledge on the basic pathogenetic processes is translated into drug development strategies that are reaching the breast cancer clinic.