Follicular lymphoma (FL) is a neoplasm derived from follicular germinal center cells. Like the normal components of this lymphoid structure, FL cells interact with various immune cells, such as the follicular helper T cells, suppressor regulatory T cells, dendritic cells, and histiocytes, that define the tumor microenvironment. Gene expression studies have shown that the nature of the tumor microenvironment predicts survival in patients with FL and may influence the response to immunotherapy and risk of transformation. The immune system may either promote or constrain tumor cell development, depending on the relative distribution and activation status of various cell subpopulations. The prognostic value of germline genetic variants of some immune genes suggests that the host genetic background may also influence the biology of FL. Some efforts have been carried out to validate those findings and provide clinical tools that may be used at the time of diagnosis.