Polymeric nanoparticulate carriers play an important role and holding a significant potential for the development of novel immunomodulatory agents as easily they are taken up by antigen presenting cells. They allow an enhanced antigen stability, better immunogenicity and immunostimulatory effect with sustained and controlled release of the antigen to the target sites. Better information and vital understanding of mechanism of action, interaction of such vectors with the APCs and dendritic cells and antigen release kinetics in immunomodulatory effects, and improved knowledge of their in vivo fate and distribution are now needed, those collectively would speed up the rational strategies of nanoparticles as carriers for vaccines and other protein antigens. The evolution of such innovative adjuvants for protein and DNA immunizations are an exciting and growing zone in immunology, which may enhance the clinical outcomes in many infectious and non-infectious diseases. This review summarizes the recent advances in nano-vaccinology with polymeric (especially biodegradable) carriers, their methods of preparation, surface modification, their interaction with antigen presenting cells, release of antigens, its kinetics and mechanism in the delivery of vaccines via non-invasive routes.