Vaccines delivered to the mucosal tissues can mimic natural infections and protect the first site of infection. Thus, oral delivery is becoming the most preferred mode of vaccination. Vesicular carrier systems (liposomes & niosomes) are one of the potential candidates for vaccine delivery by the oral route. However, oral vaccines have to overcome several barriers such as the extremely low pH of the stomach (instability in gastrointestinal (GIT) environment), the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine makes it less applicable to be used for oral immunization. This necessitates larger and more frequent doses of antigens for vaccination. Modified drug delivery systems such as a lipid vesicle containing bile salts (bilosome), which prevents antigen degradation and enhances mucosal penetration are now under investigation of oral delivery of vaccines. This paper is briefly focused on new generation bilosomes, mechanism of working, stability aspects, and in-vivo efficacy. Based on the studies, it was observed that bilosomes exhibits best systems for oral immunization. Further to this, surface engineered bilosomes are more effective that bilosomes as such in various animal models and there is need of clinical trials to study the safety and efficacy of bilosmes. Similarly, more research to be done on scaling up factors for bilosmal systems to hit the commercial market.