Numerous studies have demonstrated that targeting immunogens to Fcgamma receptors (FcgammaR) on antigen (Ag)-presenting cells (APC) can enhance humoral and cellular immunity in vitro and in vivo. FcgammaR are classified based on their molecular weight, IgG-Fc binding affinities, IgG subclass binding specificity, and cellular distribution and they consist of activating and inhibitory receptors. However, despite the potential advantages of targeting Ag to FcR at mucosal sites, very little is known regarding the role of FcR in mucosal immunity or the efficacy of FcR-targeted mucosal vaccines. In addition, recent work has suggested that FcRn is present in the lungs of adult mice and humans and can transport FcRn-targeted Ag to FcgammaR-bearing APC within mucosal lymphoid tissue. In this review we will discuss the need for new vaccine strategies, the potential for FcR-targeted vaccines to fill this need, the impact of activating versus inhibitory FcgammaR on FcR-targeted vaccination, the significance of focusing on mucosal immunity, as well as caveats that could impact the use of FcR targeting as a mucosal vaccine strategy.