Abstract: Targeting of drugs and bioactives to lymphatic system is very challenging and it depends upon the complex physiology of the lymphatic system. Targeting helps in achieving the aim of direct contact of drug with the specific site, decreasing the dose of the drugs and minimising the adverse effects caused by them. Use of nanosystem has promoted the lymphatic targeting; but still there are challenges of detecting specific sites, maintaining desired action, crossing all the physiological barriers. These hurdles could be overcome by the use of modified nanosystems achieved by the surface engineering. This review provides a summation of physiology of lymphatic system, different physicochemical parameter and their effect on lymphatic system, solute uptake by lymphatic system, different lymphatic targeting areas, strategies for surface engineering, different techniques of surface modification, detail of work done related to the drug delivery systems for lymph targeting like liposomes, nanoparticles, nanocapsules etc. This review will provide a platform for researchers working in this area of treating abnormalities related to lymphatic system with new approach of surface modification of various novel nanosystems.