Recognizing major neuroanatomical associations in the lower extremities is important to avoid complications associated with venous insufficiency procedures. The saphenous nerve could be inadvertently blocked with the tumescent anesthesia of a Cockett’s I perforator. Most concerning, it could also be affected by thermal injury when ablating the GSV below the knee. The tibial and sural nerves are also exposed to thermal injury if anatomical landmarks are not considered when performing superficial venous thermal ablation procedures. The common peroneal nerve could potentially be at risk of trauma during microphlebectomy when running superficial to the lateral aspect of the fibular head. Conversely, direct intervention to refluxing veins and venous varicosities along the sciatic and tibial nerves has shown significant improvement in polyneuropathy symptoms.