Since their discovery in 1973, dendritic cells (DCs) have gained strong interest from immunologists because of their unique capacity to sensitize naive T cells. There is now strong evidence that cells of the dendritic family not only control immunity but also regulate responses to self and non-self, thereby avoiding immunopathology. These two complementary functions are critical to ensure the integrity of the organism in an environment full of antigens. How DCs display these opposite functions is still intriguing. Here, we review the role of DC subsets in the regulation of T-helper responses in vivo.