Histone deacetylases (HDACs) are part of the epigenetic machinery, and, as such, are intricately involved in genes expression. HDAC6 is a unique isoform among the HDACs family through its enzymatic and non-enzymatic partners, but also through its structural organization. It is involved in cell motility, immunomodulation, and in the misfolded proteins degradation in the aggresome pathway. Selectively targeting HDAC6 has a particular interest in onco-hematology, in combination with other oncodrugs. Using in vitro and in silico techniques (enzymatic study, protein-protein interaction, ELISA, MST, molecular docking, pharmacophore modeling and molecular dynamics simulations), this thesis aims at exploring the molecular requirements to reach HDAC6 selectivity, and demonstrates that relevant selectivity can be achieved without altering the catalytic activity.