The specificity of HDACis for HDAC isoforms has been recently reclassified using sophisticated chemoproteomics and chemical phylogenetic approaches, revealing that HDACis have surprising affinity for both HDACs and individual HDAC-dependent multiprotein complexes (, ). This new specificity is shown for class I HDAC1, -2, -3, and -8 as well as class IIb HDAC6 and -10; specificity is calculated from average KDapp values generated by Bantscheff et al. and Bradner et al. (, ). Illustration based on data from Deubzer et al. (), Bolden et al. (), Bantscheff et al. (), and Bradner et al. (). BHC80, BRAF35-HDAC complex protein; CHD4, chromodomain helicase DNA binding protein 4; CoREST, REST corepressor 1; LSD1, lysine-specific demethylase 1; MTA, metastasis-associated protein; MBD, methyl-CpG binding domain protein; NuRD, nucleosome remodeling and deacetylase; RbAp46, retinoblastoma-binding protein p46; Sap30, Sin3A-associated protein, 30 kDa; SDS, serine dehydratase; TBL1X, transducin β-like 1X-linked; TBL1XR1, transducin β-like 1 X-linked receptor 1; GPS2, G protein pathway suppressor 2.