Nowadays, antimicrobial resistance (AMR) is a global health and development threat with three main causes such as the misuse and overuse of antimicrobial consumption, poor patient adherence to therapies, and the limited numbers of new drugs under development. This work main objective is to illustrate the current antimicrobial resistance situation in the European Union during the last decade and the main challenges to fight it. WHO published a Global Priority Pathogens List comprising twelve antibiotic-resistant priority bacteria that pose the greatest threat to human health with increasing trends observed in E. coli and K. pneumoniae. Acinetobacter spp. possesses high resistant percentages of isolates while significantly decreasing trends have been observed with P. aeruginosa. Other recent concern bacteria are methicillin-resistant S. aureus (MRSA) vancomycin-resistant Enterococci (VRE) which are associated with an increased risk of infection and mortality. Strategies to fight AMR are the identification of new potential antimicrobial targets and/or of new chemical entities that hit bacterial non-essential targets. Combination therapies of existing antibiotics and smart antibiotic adjuvants are in great demand, however it is challenging as the research and development process is time-consuming requiring investment from the pharmaceutical industry. AMR will continue to be one of the main threats for global health, which will require significant efforts at different social levels. Therefore, the identification of new strategies to limit or to overcome the occurrence of resistance strains will be a long journey, where antibiotic adjuvants counteracting antibiotic resistances will cover a significant area of the AMR fields.