Liposomes have been proposed as carriers for the delivery of therapeutic and diagnostic agents to the lymphatic system. Subcutaneous (s.c.) injection is the route of administration most extensively studied for this purpose. Decisive factors influencing lymphatic absorption and lymph node uptake of s.c. administered liposomes are liposome size and the anatomical site of injection. Generally, other factors such as lipid composition, charge and the presence of a hydrophilic PEG-coating on the liposome surface do not substantially affect lymphatic absorption and lymph node uptake of s.c. administered liposomes. Studies on the intranodal fate of liposomes demonstrate that phagocytosis by macrophages is the most important mechanism for lymph node uptake of liposomes. The observation of relatively high uptake of liposomes in regional lymph nodes after s.c. administration has stimulated research on lymphatic targeting of liposomes for diagnostic and therapeutic applications.