The immune system utilizes sophisticated cellular surveillance mechanisms to maintain the integrity of the multicellular host. Adaptive immunosurveillance in particular constitutes a powerful branch of the immune system that houses the capacity to mount exquisitely specific responses against a diverse array of foreign antigens. Central to the development of adaptive immunity is the activation of T and B cells. Upon antigen engagement, T and B cells have been observed to undergo striking changes in their migratory status and distribution within secondary lymphoid organs, a phenomenon that is to a large extent controlled through their altered responsiveness to homeostatic T- and B-zone chemokines. Changes in their chemokine receptor expression and/or sensitivity to their respective ligands assist in bringing rare antigen-specific T and B lymphocytes, dendritic cells and CD4+CD3− accessory cells together. Cognate interaction between these cells at the T–B junction can support the generation of extrafollicular foci of antibody producing plasma cells and the formation of germinal centers. Such T-dependent antibody responses are highly dependent on the functional properties and activity of a specialized subset of CXCR5+ICOS+ CD4 T cells referred to as T follicular helper cells (TFH). This review presents an overview of some of the defining characteristics of this subset of T-helper cells and the chemokine receptors and their ligands that help dictate the migratory activity of TFH cells within secondary lymphoid organs.