Histone deacetylases 6 (HDAC6) has emerged as a promising target for the treatment of various human diseases including cancer, neurodegenerative disease and immunology due to its unique structure, substrate and biological functions. HDAC6 is involved in cell motility, cell survival, cell cycle progression, developmental events, prognosis as well as protein degradation and the involvement of HDAC6 in multiple biological processes has gained lots of attention. There is increasing interest in HDAC6 and its selective inhibitors. More than twenty years of synthetic efforts have developed various HDAC6 selective inhibitors with different Cap, linker and ZBG. This review will summarize recent research data regarding HDAC6 and various HDAC6 selective inhibitors.