Mucosal immunization has potential benefits over conventional parenteral immunization, eliciting immune defense in both mucosal and systemic tissue for protecting from pathogen invasion at mucosal surfaces. To provide a first line of protection at these entry ports, mucosal vaccines have been developed and hold a significant promise for reducing the burden of infectious diseases. However, until very recently, only limited mucosal vaccines are available. This review summarizes recent advances in selected aspects regarding mucosal vaccination, including appropriate administration routes, reasonable formulations, antigen-sampling and immune responses of mucosal immunity, and the strategies used to improve mucosal vaccine efficacy. Finally, the challenges of developing successful mucosal vaccines and the potential solutions are discussed.