Multiple myeloma is a hematological malignancy consisting of abnormal plasma cells that uncontrollably proliferate in the bone marrow leading to end-organ damage. It accounts for approximately 19% of newly diagnosed blood malignancies and it is the second most prevalent hematological cancer after non-Hodgkin lymphoma. Despite the expansion of available drugs, current therapies still bring important side effects and practically all patients undergo relapse and refractory events. Therefore, there is a need to improve and refine the therapeutic options. Histone deacetylases were proposed as possible therapeutic targets, but the non-selective inhibition of this group of proteins led to serious adverse events. Histone deacetylase 6 contains a C-terminal zinc-finger ubiquitin-binding protein domain able to recognize ubiquitinated proteins and activate the aggresome pathway. Therefore, it has been proposed as a potential target responsible for resistance to conventional proteasome inhibition therapy. A two-residue mutation inactivating this zinc-finger domain disrupted its interaction with ubiquitin in a cell-free assay. Moreover, a RPMI 8226 multiple myeloma cell line containing this mutation showed a decreased aggresome formation, cell growth and a dysregulated gene expression profile. Genes affected upon this mutation were mainly related to immunological and cell adhesion functions. These results led to the design of small molecules predicted to inhibit the zinc-finger ubiquitin-binding domain, but they did not exert any antiproliferative activity in multiple myeloma cells alone or in combination with proteasome inhibitors. The work presented in this thesis focuses on histone deacetylase 6 as a potential target against multiple myeloma and exposes other proteins that could be relevant in the pathogenesis of the disease.