Currently, the emergence of multidrug resistant microorganisms as Acinetobacter baumannii and Mycobacterium tuberculosis as well as new drug resistant forms of Neisseria gonorrhoeae in conjunction with the evolving of resistance genes as the KPC (class A Klebsiella pneumoniae) and NDM-1 (New Delhi metallo-β-lactamase 1) carbapenemases are a public health threat that requires great efforts in prevention, treatment and diagnosis. For that reason, the InterAcademy Panel and InterAcademy Medical Panel statement (IAP-IAMP) included in their Global recommendations call for action to tackle antimicrobial resistance under the following item “Encourage industry innovation and public-private collaborative research and development programs for therapeutics, diagnostics, and vaccines”. In this way, the development of novel antimicrobial drugs is not only necessary, is a priority the search and development of new pharmacological strategies for prevent antimicrobial resistance emergence, these strategies should have the ability of improve the current anti-infective therapy in combination and recuperate the susceptibility of multidrug-resistant strains to the antibiotics. Thereupon, the introduction of screening platforms in a rational in vitro antimicrobial adjuvants drug discovery program is an important approach that will allow the detection of new chemical entities that can inhibit resistant mechanisms specifically and without side effects, looking for increase the microbicidal effect and prevent the development of subsequent mutations to anti-infective therapy. The aim of this review is to explore antibiotic adjuvants as a therapeutic plan of action that can be developed for the discovery of new compounds that make bacteria more susceptible to anti-infectives by improving their efficacy.