B and T lymphocytes recognize antigens with high specificity, but neither initiate immune responses, nor decide their types. These functions rest upon dendritic cells (DCs), which can determine and maintain Th1/Th2 polarization. Immune responses are thus dependent on the DC subset, the receptors that recognize each pathogen and the microenvironment. Microbes employ an array of mechanisms to evade and disrupt DC functions; some even hijack DCs for transport around the body. Our progress in the understanding of DC physiology will hopefully help us create the necessary vaccines to counteract the infectious agents that still plague mankind. Immune responses to microbes ultimately depend on the way that dendritic cells recognize and respond initially.