In this review, we focus on the function of CD40-CD40L (CD154) interactions in the regulation of dendritic cell (DC)-T cell and DC-B cell crosstalk. In addition, we examine differences and similarities between the CD40 signaling pathway in DCs and other innate immune cell receptors, and how these pathways integrate DC functions. As research into DC vaccines and immunotherapies progresses, further understanding of CD40 and DC function will advance the applicability of DCs in immunotherapy for human diseases.