Simple SummaryThe lymphatic vascular system drains fluid, solutes and cells from the interstitial tissue surrounding the cells and subsequently returns the newly formed lymph back into blood circulation. Through their continuous drainage, lymphatic vessels maintain the adequate volume and composition of the tissue environment around the cells, guaranteeing their physiological behavior. Secondary lymphedema is a complex pathology whose progression depends upon an impairment of the lymphatic draining function, developing because of demolishing oncological surgeries, radiation, blood vascular malformations or surgical excision of local lymph nodes. In such cases, removal, obstruction, or impairment of the lymphatic vasculature cause the accumulation of fluid, solute and cell debris into the tissue, with progressive swelling, functional impairment and physical distress of the patient. The present review illustrates various cases of secondary lymphedema of increasing severity and the newest therapeutic solutions, spanning from indication of adequate body posture to physical therapy, to the newest and least invasive microsurgical approaches developed with long term satisfactorily results in the treatment of secondary lymphedema.AbstractSecondary lymphedema is a complex pathology which is very impairing to the patient, consisting of fluid accumulation in the tissue, accompanied by alteration of the interstitial fibrous tissue matrix, deposition of cellular debris and local inflammation. It develops mostly in limbs and/or external genitals because of demolishing oncological surgery with excision of local lymph nodes, or it may depend upon inflammatory or infective diseases, trauma, or congenital vascular malformation. Its treatment foresees various approaches, from simple postural attitude to physical therapy, to minimally invasive lymphatic microsurgery. This review focuses on the different types of evolving peripheral lymphedema and describes potential solutions to single objective symptoms. Particular attention is paid to the newest lymphatic microsurgical approaches, such as lymphatic grafting and lympho-venous shunt application, to successfully heal, in the long term, serious cases of secondary lymphedema of limbs or external genitals. The presented data also emphasize the potential role of minimally invasive microsurgery in enhancing the development of newly formed lymphatic meshes, focusing on the need for further accurate research in the development of microsurgical approaches to the lymphatic vascular system.