Immunotherapy has revolutionized cancer therapy, yet its durability and broad applicability need to be improved. Tertiary lymphoid structures (TLS) are clusters of specialized immune cells (B cells, T cells, dendritic cells, stromal cells, etc.) that form in and around a tumor. TLS coordinate with immunotherapeutic response in multiple solid tumors, yet their presence is highly variable across cancer types and between patients. These structures arise in response to inflammation and antigen to help the body coordinate a directed antitumor immune response. In this chapter, we compare TLS development with features of secondary lymphoid organs (SLO) as they are well-orchestrated immunological hubs that are better understood than TLS. We describe key factors (cytokines and chemokines) and cellular populations (stromal cells and high endothelial venules) involved in TLS development. Further, we explore attributes of a mature and functional TLS (follicular dendritic cell networks and germinal centers). In the second part of the chapter, we compare select solid tumors that have been assessed for TLS formation and maturity and indicate how these features impact prognosis, elaborating on mechanism of action for TLS. In summary, this chapter presents compelling evidence that TLS are elegantly regulated and complex structures which may be exploited to promote patient survival and response to immunotherapy.