Understanding the regulation of antibody production and B-cell memory formation and function is core to finding new treatments for B-cell-derived cancers, antibody-mediated autoimmune disorders, and immunodeficiencies. Progression from a small number of antigen-specific B-cells to the production of a large number of antibody-secreting cells is tightly regulated. Although much progress has been made in revealing the transcriptional regulation of B-cell differentiation that occurs during humoral immune responses, there are still many questions that remain unanswered. Recent work on the expression and roles of histone modifiers in lymphocytes has begun to shed light on this additional level of regulation. This review will discuss the recent advancements in understanding how humoral immune responses, in particular germinal centers and memory cells, are modulated by histone modifiers.