It is well accepted that T cell responses are integral in providing protection during pathogenic infections. In numerous tissues, T cell responses are generated to combat infection. Typically, these T cell responses are primed in draining lymph nodes (LN) by dendritic cells (DC) that have migrated from the infected tissue. Previously, it was thought that after the initial encounter between DC and T cells in the LN, the T cells underwent a programmed response. However, it has become increasingly clear that direct interactions between DCs and T cells in infected, peripheral tissues can modulate the activation, effector function, tissue residence, and memory responses of these T cells. This review will highlight the contribution of local, direct DC: T cell interactions to the regulation of T cell responses in various tissues during inflammation and infection .