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Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology focuses on the critical questions currently debated in the field of immune memory and vaccination. Topics include the plasticity of memory CD4 T cells, the formation of germinal centers by memory B cells, the contributions of natural killer cells to immune memory, and the influence of commensal microbiota on immune responses. Several contributors respond to each question, providing a variety of fresh, concise perspectives on each topic.