The initiation, magnitude and duration of an immune response against antigens are a tightly regulated process involving a dynamic, orchestrated balance of pro- and anti-inflammatory pathways in immune cells. Such a delicate balance is critical for allowing efficient immune response against foreign antigens while preventing autoimmune attack against self-antigens. In recent years, much effort has been devoted to understanding immune evasion by cancer cells. Also, significant advances have been made in mechanistically understanding the role of pro- and anti-inflammatory cytokines in the regulation of immune responses against antigens, including those expressed by tumors. However, we still know very little about the regulation of inflammatory/anti-inflammatory genes in their natural setting, the chromatin substrate. Several mechanisms have been identified to influence chromatin flexibility and allow dynamic changes in gene expression. Among those, chromatin modifications induced by acetylation and deacetylation of histone tails have gained wide attention. In this study, we discuss the role of histone deacetylases in the transcriptional regulation of genes involved in the inflammatory response and how these enzymes coordinate the dynamic expression of these genes during an immune response. This emerging knowledge is opening new avenues to better understand epigenetic regulation of inflammatory responses and providing new molecular targets for either amplifying or ameliorating immune responses.