Sepsis is the leading cause of death for critically ill patients in recent years. Dendritic cells (DCs) are important antigen-presenting cells and play a key role in immune response by regulating the innate and adaptive immunity. The number of DCs, the differentiation of monocytes into DCs, and the levels of surface molecules associated with the function of DCs are changed in the development of sepsis. There are many mechanisms involved in the alterations of DCs during sepsis, including the induction of apoptosis, reactive oxygen species generation, activation of the Wnt signaling pathway, epigenetic regulation, and variation in Toll-like receptor-dependent signaling. In this review, we present the classifications of DC subsets and mechanisms involved in the alterations of DCs in sepsis, as well as further discuss the therapeutic strategies targeting DCs in sepsis to improve the aberrant immune response and prolong the life during sepsis progression.