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It has now been *20 years since the original Lymphatic Continuum conference was convened, and this continuum has transitioned from a compelling concept to a reality. The explosive growth in our comprehension of lymphatic genetics, development, and function has expanded and modified our traditional views regarding what is, and is not, lymphatic disease. Groundbreaking investigations over the past decade have now defined a large and growing list of pathological conditions in which morphological or function lymphatic alterations can be identified. This list includes atherosclerosis and dyslipidemia, hypertension and other cardiovascular diseases, inflammation and inflammatory bowel disease, obesity, narrow angle glaucoma, and, most recently and compellingly, neurodegenerative disease. The sometimes overlapping but largely disparate nature of these various aforementioned disease categories suggests that the presence, or absence, of structural or functional lymphatic derangements may represent a previously unrecognized unifying influence in the maintenance of health and the promotion of disease. Future investigation of lymphatic mechanisms in disease will likely continue to elucidate the influences of lymphatic dysfunction, perhaps subtle, that can invest other, seemingly unrelated, diseases. In future, such discoveries will provide mechanistic insights and may potentiate the development of a new lymphatic-based approach to human disease diagnosis and therapeutics.