Specific defense mechanisms against pathogens are fulfilled by different subsets of nonmucosal conventional dendritic cells (DCs), including migratory Langerhans cells (LCs), dermal DCs, and resident CD8⁺ and CD8⁻ DCs found in lymphoid organs. Dermal DCs capture antigens in the skin and migrate to lymph nodes, where they can transfer the antigens to CD8⁺ DCs and activate CD4⁺ T cells. Differential antigen-processing machinery grants CD8⁺ DCs a high efficiency in activating CD8⁺ T cells through crosspresentation, whereas CD8⁻ DCs preferentially trigger CD4⁺ T cell responses. Recent findings have revealed the important role played by monocyte-derived DCs (mo-DCs), newly formed during infection, in activating CD4⁺ and CD8⁺ T cells, regulating immunoglobulin production, and killing pathogens. However, a number of controversial issues regarding the function of different DC subsets during viral, bacterial, and parasitic infections remain to be resolved.