Dendritic cells are a heterogeneous population of bone marrow-derived cells present in most peripheral tissues. These cells are able to capture and present antigens to T cells. Such presentation can lead to two opposite outcomes: potent activation (immunogenicity) or inhibition (tolerance) of the immune response. The fine regulation of these two distinct functions is not completely understood to date. In this review, we discuss three potential variables that may influence dendritic cell function: the origin of dendritic cells, their maturation state, and their capture properties. Each hypothesis is illustrated with examples in the field of transplantation. Lastly, the criteria necessary for proposing tolerogenic dendritic cells to promote engraftment and long-term allograft survival are discussed.