Over the past decade, it has become apparent that B cells acquire antigens primarily from membrane surfaces and that uptake is an active process involving a synapse between the B cell receptor, coreceptor, and the antigen surface. However, understanding how antigens are delivered to follicular dendritic cells (FDC), which are the primary depot for B cell antigen within the lymph node follicles, is only recently beginning to be dissected. The application of fluorescent-based imaging techniques such as multiphoton intravital microscopy to visualize trafficking of B cells and antigens into draining lymph nodes has provide insights that would not otherwise be made. At least three novel pathways for transport of lymph-borne antigens to the B cell compartment have been identified. Based on these studies, a new paradigm of how lymphocytes and antigens traffic within the peripheral lymph nodes is evolving. Understanding how the physical properties of the antigen influences its uptake and processing could be relevant in the design of new vaccines.