Chronic venous disease, a disorder involving venous return from the legs, is a growing epidemic in the developed world. Numerous studies have been conducted in the past two decades in an attempt to elucidate its underlying pathophysiology. Many theories have been proposed to address the profound inflammatory dysregulation, with the majority focusing on fibrin trap, inflammatory trap, cytokines, growth factors, and matrix metalloproteinases. Although many of these theories have obtained great momentum, much of the data are contradictory. Moreover, many treatments built on these theories have claimed overwhelming success despite insufficient evidence. At the same time, there are few reviews that critically analyze and evaluate these data. Therefore, in this paper, we will provide summaries of the background data and evolution of these theories and examine their supporting evidence.