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Venous leg ulceration (VLU) is a medically, financially, and psychologically debilitating disease for patients and a financial burden for the health care system. Of all dermatologic diseases, VLU generates the highest cost. The purpose of this manuscript is to review the current guidelines on the diagnosis and management of VLU with an emphasis on novel approaches. Two novel approaches to VLU diagnosis have been proposed in 2019 including voltammetric analysis to determine leg ulcer etiology, identify infection, and predict clinical course, and the use of dynamic optical coherence tomography to image blood capillaries of the peri-wound skin. Novel approaches to management include the use of trichloroacetic acid and low-frequency ultrasound debridement, growth factors harvested from human amniotic membrane or platelet-rich plasma, low-level laser therapy, and low-energy light therapy. With shifting demographics toward an aging population, sedentary lifestyles, an increased prevalence of obesity, and the emergence of chronic diseases, VLU will likely continue to be a significant burden to patients and the health care system. Treatment should not purely be focused on healing, but should take a holistic approach, incorporating nutrition and well-being. The gold standard for the prevention and treatment of VLU is compression therapy and should be utilized with the TIME strategy which contributes to the stimulation of natural healing mechanisms and includes the following: Tissue debridement, Infection and inflammation control, Moisture balance, and Epidermization stimulation.