FOX O family transcription factors are important for differentiation and function of multiple cell types. In B lymphocytes they play a critical role. The activity of FOXOs is directly regulated both by signaling from B cell receptor (BCR) and cytokine receptors. FOXO1 action controls the transition between differentiation stages of B cell development. In comparison to other FOXO family members, FOXO1 plays a superior role in the regulation of early stages of B-cell differentiation. Although being known as a negative regulator of cell proliferation and therefore potential tumor suppressor, FOXO1 is downregulated only in Hodgkin lymphoma (HL) subtypes. In non-Hodgkin lymphoma (NHL) entities its expression is maintained at significant levels, raising the question on the role of FOXO-transcription factors in the proliferation and survival programs in the process of B cell differentiation as well as their contribution to the oncogenic programs of B-cell lymphomas. In particular, we discuss molecular mechanisms that might determine the switch between pro-apoptotic and pro-survival effects of FOXO1 and their interplay with specific differentiation programs.