SummaryCD38 is a 45 kDa transmembrane receptor expressed in B lymphocytes and other cells from the immune system. It is involved in apoptosis, cell activation, differentiation, and proliferation. CD38 has been used extensively to classify various subpopulations of lymphocytes in both humans and mice. It has also been used as a marker of poor prognosis in some lymphoid pathologies. However, CD38 is not a marker but rather an ectoenzyme and a receptor, where it performs several functions. The CD38 signaling pathway has only been partially studied in various cells of the immune system, where apparently the signaling is different depending on the lineage and differentiation state of the cell, leading to distinct outcomes. In this review, we provide an overview of well-established roles of CD38 signaling B lymphocytes from mice. We also discuss areas that need further clarification to get a broader image of how CD38 performs different functions in B cells and to understand its role in B lymphocyte biology under normal versus pathological conditions.