A strong line of evidence for the potential for chemotherapy treatments to cause cognitive impairments comes from experiments examining the effects of chemotherapy drugs in cancer-free laboratory animals. These studies have shown, repeatedly, that laboratory animals treated with chemotherapy drugs develop dose-dependent, persistent and broad impairments on tests designed to assess memory, executive function, and attention. In our own laboratories, we have reported the long-term effects of metabolic inhibitors, platinum drugs, and taxanes on cognitive function. However, an advantage of these preclinical models is the potential to rapidly screen potential treatments. In this talk, I will discuss our evidence that increased physical activity and exercise can both prevent and reverse the cognitive impairments caused by chemotherapy drugs, and can also prevent the development of painful neuropathies during treatment.