Vaccines are formulated to generate strong immune responses against administered antigens thereby providing long-term immunity,especially against microbial infections. To achieve this goal, safe and optimal vaccines are designed by developing new generationvaccines with efficacious adjuvants. These vaccines are mainly based on recombinant forms of protein subunits that are purified frommolecular constructs of microbial agents with known chemical structures. However, these vaccines are poorly immunogenic and thuscannot induce an appropriate protective immune response. Therefore, to increase in vivo efficacy and stability of these vaccines, a safeand improved adjuvant is essential. Adjuvants in human vaccine formulations should be non-toxic, biologically inert, biocompatible,biodegradable as well as capable of facilitating the induction of antigen-specific immune responses. Currently, alum compounds are theonly adjuvants approved in human vaccines. Though many clinically tested adjuvants more potent than alum are available, safety andregulatory concerns preclude their use for human applications. To address life-threatening pandemic diseases and ever evolving drug-resistant microbial infections worldwide, designing vaccines with safe and efficacious adjuvant is a major challenge for the scientificcommunity that needs to be addressed systematically. © 2014 OMICS Group