Zn(II) is an essential metal ion in living organisms, playing a wide variety of roles as a structural, regulatory or catalytic cofactor in proteins, that is able to interact with approximately 10% of the entire proteome in humans [1]. As is the case for most transition metal ions, high Zn(II) levels are toxic. Therefore, organisms have developed a series of mechanisms to regulate Zn(II) concentrations and to ensure proper metal uptake by metalloproteins [2]. These mechanisms involve specific metal sensor proteins, import and export machineries that allow subcellular compartmentalization and a pool of small molecules and/or proteins that are able to bind excess Zn(II) [2]. As a result, there is rarely free Zn(II) within cells and biological fluids [3]. Bacterial pathogens require transition metal ions during infection to achieve an optimum colonization level and to activate a variety of virulence factors. This condition is exploited by the human host, which sequesters these metal ions in a process generally termed ‘nutritional immunity’, originally coined to account for the role of iron ions [4]. This concept has been more recently extended to also describe the competition for Mn(II) and Zn(II) [5]. The latest mechanism is based on the action of the neutrophil protein calprotectin, which tightly binds Mn(II) and Zn(II), thus inhibiting bacterial growth [6]. Therefore, a tight competition takes place between the host and the pathogen for capturing Zn(II) ions, which can significantly affect bacterial infection processes. In addition to that, antibiotic resistance can also be affected by Zn(II) sequestration, as recently reported for a multidrug-resistant Acinetobacter baumannii strain, whose susceptibility to carbapenems was increased in the presence of a Zn(II)-chelating agent [7]. Multiple resistance mechanisms against β-lactam antibiotics involve Zn(II) ions as essential factors. For example, resistance to imipenem in Pseudomonas aeruginosa is Zn(II)-dependent through the downregulation of porin OprD [8]. However, the most outstanding resistance mechanism towards β-lactam antibiotics involving Zn(II) ions is the expression of met-allo-β-lactamases (MβLs). MβLs, unlike classical serine-β-lactamases, are metalloenzymes requiring one or two Zn(II) ions for their activity [9,10]. MβLs gained importance since the 1990s as the principal mechanism of resistance against carbapenems, one of the most valuable antibiotics nowadays for treating multiresistant pathogens. MβLs are actually broad-spectrum enzymes, being able to degrade almost all classes of β-lactams (penicillins, cephalosporins and carbapenems). MβL genes have been detected in a wide variety of environmental bacteria as endogenous genes. However, their association with mobile genetic elements (often with other resistance cassettes) prompted the dissemination of MβLs genes into clinically relevant pathogens, such as P. aeruginosa or members of Enterobacteriaceae, which possess nearly pan-resistant phenotypes. Moreover, unlike most other β-lactamases, MβLs are not susceptible to any of the therapeutic β-lactamase inhibitors available, which converts them into a serious clinical threat. Outbreaks of pathogens producing the MβLs NDM-1, IMPs, VIMs or SPM-1 are increasingly common worldwide, with high rates of mortality and morbidity.