This Perspective provides an in depth look at the numerous disease states in which histone deacetylase 6 (HDAC6) has been implicated. The physiological pathways, protein−protein interactions, and non-histone substrates
relating to different pathological conditions are discussed with regard to HDAC6.Furthermore, the compounds and methods used to modulate HDAC6 activity are profiled. The latter half of this Perspective analyzes reported HDAC6 selective
inhibitors in terms of structure, potency, and selectivity over the other HDAC isoforms with the intent of providing a comprehensive overview of the molecular tools available. Potential obstacles and future directions of HDAC6 research are also presented.