Several histone deacetylases (HDACs) are involved in the regulation of forkhead box protein P3 (FOXP3) expression and function by affecting features of FOXP3 protein stability. FOXP3, a forkhead family transcription factor specially expressed in regulatory T (Treg) cells, controls the expression of many key immune-regulatory genes. Treg cells are a population of T lymphocytes that have critical roles in the immune system homeostasis and tolerance to self and foreign antigens, the body's response to cancer and infectious agents. FOXP3 forms oligomeric complexes with other proteins, the components of which are believed to be regulated dynamically. In addition, HDAC activities influence FOXP3 interactions with other partners to form transcriptional regulatory complexes. By understanding the details of the biochemical and structural basis of the regulation of FOXP3 acetylation, therapeutic strategies for diseases related to Treg cells may emerge.