Cancer cells display remarkable plasticity allowing them to adapt to ever changing environments. A key feature of this plasticity is their ability to rewire core metabolic networks to provide a steady source of energy and building blocks needed for rapid growth. This demand for energy produces byproducts including reactive oxygen species (ROS) that alter the function of proteins, DNA and lipids, and if left unchecked, results in oxidative stress and impairs cancer cell viability. We now appreciate that ROS and other reactive metabolites are not just static entities within a cell, but represent dynamic signaling molecules that alter cellular and organismal physiology. Despite decades of research, we know surprisingly little about about ROS sensing and signaling and how this class of molecules regulates protein function within the cell. Our long term goals are to understand how cells respond to altered metabolic states and to pharmacologically modulate these pathways in diseases where they are deregulated.