Copper is an essential micronutrient for most living beings including bacteria. This is mainly due to essential roles of catalytic Cu-centers in enzymes. However, an excess of Cu is toxic and thereby used over centuries as a powerful antimicrobial agent. Bacteria developed several systems to detect Cu and protect themselves from high intracellular Cu concentration, namely via Cu-extrusion and/or Custorage. Several Cu-detoxification systems have been described and new ones are still being discovered. Progress has also been made in understanding the molecular mechanism of Cu-toxicity by identifying target macromolecules. Nevertheless, the importance of each mechanism is bacteria- and environment-dependent paving the way for new findings. The chemical reactivity of Cu can be modulated by its coordination environment in a complex with a ligand (L) and this opens large opportunities to tune the Cu-ligand complexes (Cu-L) via ligand design. For instance, boosting the toxicity of Cu ions toward bacteria was promoted by several small organic ligands. These ligands can make Cu-L complexes with different properties in terms of coordinating atoms (S, N, O), Cu to L stoichiometry, ligand denticity, thermodynamic stability, kinetic inertia and redox potential. However, one common feature shared by Cu-L complexes which efficiently boost Cu-toxicity is the ability of Cu-L to cross the two bacterial membranes and to release the Cu in the cytosol. If this property is required to improve bacteria killing is not clear yet, but considering the ever-growing resistance of bacteria, it would be interesting in the future to try to boost Cu-toxicity via unprecedented mechanisms.