Diagnostic tests that currently direct patient therapy in cancer and other diseases are more typically performed at the genetic level, despite the fact that the beneficial response to drugs and the development of resistance are rooted in the proteins that comprise the cell’s signaling pathways. We argue that this is a major gap, as proteomics can be used to understand how cells respond to inhibitors, thereby identifying patients who are responding positively at the molecular level, as well as patients who are developing resistance through the reorganization of the cell’s signaling network.