Painful peripheral neuropathy is the major dose-limiting side effect of several first-line, highly effective chemotherapeutic agents. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies (CIPPN). Furthermore, several analgesics with established efficacy in other painful neuropathies have failed to show any efficacy in double-blind, placebo-controlled RCTs of patients with CIPPN. Therefore understanding the causal mechanisms for CIPPN is essential to enable analgesic development in this area of substantial unmet clinical need. Several reports using rodent models of CIPPN have indicated evidence for mitochondrial dysfunction and reactive oxygen species (ROS) to be contributory factors to this pain syndrome. Our research team at King’s College London, is examining the contribution of mitochondrial function before, during and at the resolution of paclitaxel-induced painful peripheral neuropathy to correlate cellular mechanisms to whole animal behaviour. During this talk, I will discuss some of our latest data on ROS and mitochondrial function during paclitaxel-induced painful peripheral neuropathy.