Cytotoxic T lymphocytes (CTLs) generally recognize antigens endogenously synthesized within the cells and presented in the form of peptides on class I molecules. However, a large body of evidence suggests that dendritic cells (DCs) have the capacity to capture and deliver exogenous antigens into the major histocompatibility complex (MHC) class I processing pathway. In this paper, we discuss this function, defined as cross-presentation, and how it is directed, particularly in inducing T cell tolerance, and how it requires special activating signals (such as CD40 ligand) to transform into a mechanism that provides either protective immunity or autoimmunity.