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.