Secondary lymphoid organs (SLO) are crucial structures for immune-surveillance and rapid immune responses allowing resident lymphocytes to encounter antigen-presenting cells that carry antigens from peripheral tissues. These structures develop during embryonic life through a tightly regulated process that involves interactions between haematopoietic and mesenchymal cells [1,2]. Importantly, this morphogenesis potential is maintained throughout life since in chronic inflammatory conditions novel “tertiary lymphoid organs” can be generated by processes that are reminiscent of embryonic SLO development. In this review we will discuss early events in SLO morphogenesis, focusing on haematopoietic and mesenchymal cell subsets implicated on the development of lymphoid organs.