INTRODUCTION: The respiratory tract is an attractive target for the delivery of vaccine antigens. Potential advantages of drug delivery by means of the pulmonary route include accessibility, non-invasiveness, ease of administration, and the possibility to reach an elaborate mucosal network of antigen-presenting cells. AREAS COVERED: This review discusses current pulmonary vaccination strategies and their advantages and disadvantages. EXPERT OPINION: To improve efficiency of vaccination and develop new strategies, a well-founded knowledge about composition and characterization of antigen-presenting cell populations throughout the respiratory tract is essential. In particular, respiratory tract dendritic cells, as key antigen-presenting cells in the lung, constitute an ideal target for vaccine delivery. Furthermore, particle size is a key factor when designing new inhalable vaccines, as size determines not only deposition in different respiratory tract compartments, but also how an antigen and its carrier will interact with lung tissue components and immune cells. An increased knowledge of different respiratory tract antigen-presenting cell populations and their interactions with other components of the immune system will enable new targeting strategies to improve the efficacy of pulmonary vaccination.