Immunological memory is a hallmark of the adaptive immune system. Plasma cells and memory B and T cells collectively provide protective immunity and effective secondary immune responses to invading pathogens. Here, we discuss how mesenchymal stromal cells regulate immunological memory by organizing defined numbers of dedicated survival niches for plasma cells and memory T cells in the bone marrow and also, to a lesser extent, in secondary lymphoid organs. An understanding of the biology of mesenchymal stromal cells and their interaction with cells of the immune system is key to fully understanding immunological memory.