Pain is the leading complaint of patients with venous disease. It has a significant effect on the patient's quality-of-life. For the clinician and the researcher however it is difficult to apprehend how pain is related to the venous disease, both because of the multiple factors involved and because of the lack of any strong relationship between pain symptoms and the severity of the venous disease. Currently, several hypotheses concerning the pathogenesis of pain in venous disease have focused on the causal impact of local inflammation. Over the last five years, a large body of evidence has been accumulation showing an inflammatory reaction around varicose veins, but the precise mechanism of how inflammatory mediators interact with venous nociceptors, which might explain part of the variability in pain observed in venous disease, remains elusive, both clinically and experimentally.