While our understanding of the lymphatic system has improved substantially in the past few decades, the translation of this knowledge into improved healthcare solutions for patients suffering from secondary lymphedema has been severely limited. The challenge facing clinicians is two-fold. First, there is no reliable, affordable, diagnostic capable of detecting the disease before symptoms of the lymphedema develop and the efficacy of treatment options becomes limited. Second, our understanding of the disease pathogenesis, its risk factors, and the underlying physiologic mechanisms is still in its infancy. These two challenges go hand in hand as limited diagnostic options have hindered our ability to understand lymphedema progression, and the lack of known underlying mechanisms involved in the disease prohibits the development of new diagnostic targets. This review serves to discuss the recent developments in clinical and lab research settings of both lymphedema diagnostic technologies and our understanding of the mechanisms driving disease risk and progression. We will show how these two lines of research are synergistically working with the ultimate goal of improving patient outcomes for those suffering from this horrible disease, identifying key areas of further research that are warranted to move the field forward and provide clinical relief for this neglected patient population.