Drug-resistant bacteria are an important public health concern. They are spreading across the world, increasing mortality and morbidity rates. The misuse of antimicrobials has been central to this increase. It is therefore necessary to implement improvement measures. The Centers for Disease Control and Prevention (CDC) recommends four core actions to fight back against antibiotic resistance: Antimicrobial Stewardship Programs (ASPs); prevention of infections; tracking of antibiotic resistance; and development of new drugs and diagnostic test. In recent years very few antimicrobials have been commercialized, so several initiatives have raised in order to promote antibiotic research like Generating Antibiotics Incentives Now (GAIN) act, Innovative Medicines Initiative New Drugs for Bad Bugs (IMI ND4BB) or 10 x ’20 Initiative to develop 10 new, safe and effective antibiotics by 2020. Thanks to these initiatives, some new antibiotics have been approved recently: Dalbavancin, Tedizolid or Oritavancin, all indicated in the treatment of acute bacterial skin and skin structure infections (ABSSSI), mainly caused by Gram positive bacteria of genus Streptococcus or Staphylococcus. The landscape for Gram negative infections does not look so promising, with only a few compounds undergoing clinical trials. Other compounds in pipeline attack different pathways of resistance: aspergillomarasmine A was identified as a potent inhibitor of NDM-1, a metallo-β-lactamase (MBL) which has contributed to the rise of carbapenem resistant Gram-negative bacteria. The slow development of new antimicrobials and its misuse have trigged the current situation of emergence and spread of antibiotic resistance, emptying effective treatment and forcing the use of old antibiotics. This situation makes necessary to develop new strategies in order to overcome resistance to available antibiotics and also perform clinical trials with older drugs to improve their safety profile. In addition to actions that ensure the appropriate use of antibiotics.