The field of vaccine adjuvants has been an area of active research and development because of the need to improve the generation of protective immunity to a large number of pathogens, as well as in diseases such as cancer. Adjuvants can also help induce stronger immune responses with fewer injections, and consequently improve both the feasibility and success rate of large-scale population vaccine campaigns in developing countries. A current challenge is to identify vaccine adjuvants of various classes (cytokines, toll-like receptor ligands, etc.) with specific immune-modulating properties in order to tailor the immune response to certain pathological situations. In this issue, Van Roey et al. [Eur. J. Immunol. 2012. 42: 353–363] explore one of these challenges, namely to identify novel mucosal adjuvants. Van Roey et al. show that the pro-allergic cytokine thymic stromal lymphopoietin (TSLP) promotes a strong B-cell response with production of secretory IgA at mucosal sites. Here, we discuss the importance and limits of these findings within the broader field of vaccine adjuvants, and the potential development of TSLP as a mucosal and B-cell adjuvant in humans.