Introduction: The dissemination of multi-drug resistant bacteria (MDRB) has become a major public health concern worldwide because of the increase in infections caused by MDRB, the difficulty in treating them, and expenditures in patient care.Areas covered: We have reviewed challenges and contemporary opportunities for rapidly confronting infections caused by MDRB in the 21st century, including surveillance, detection, identification of resistance mechanisms, and action steps.Expert commentary: In this context, the first critical point for clinical microbiologists is to be able to rapidly detect an abnormal event, an outbreak and/or the spread of a MDRB with surveillance tools so that healthcare policies and therapies adapted to a new stochastic event that will certainly occur again in the future can be implemented.