Lymphatic vessels are present throughout the body, except in the central nervous system and bone marrow. The lymph nodes (LNs), spleen, and other secondary lymphoid organs (e.g., Peyer's patches) are strategically located in anatomical sites where they collect foreign antigen and antigen presenting cells to activate antigen-specific lymphocytes efficiently.1 In the peripheral tissues, specialized lymphatic capillaries—called initial lymphatic vessels—allow soluble materials and cells to enter the lymphatic system easily. The collected fluid and cells form lymph, which is transported by smooth muscle-invested collecting lymphatic vessels to the draining lymph node. The lymph node provides a highly organized microarchitecture that supports optimal immune surveillance. The “filtered” lymph fluid, as well as naive and activated lymphocytes, exit the lymph node via efferent lymphatic vessels. Lymphatic capillaries, collecting lymphatic vessels, and lymph nodes together provide protective immunity for the body. Disruptions of lymphatic function compromise immune function and result in lymphedema. In this review, we will summarize the current knowledge of how lymphatic function is altered in inflammatory states, cancer, and infection.