Maybe two centuries ago that penicillin had been discovered by Alexander Fleming and humanity was proud of them to overcome all infections, no one would think that a day would come that antibiotics become obsolete. According to the WHO global report on surveillance about antimicrobial resistance in 2014, Iran is classified among the countries with more than five multi-drug resistances on seven bacteria considered as major international concerns. Pursuant to this report, like other developing and developed countries, Iran would be exposed a tsunami of drug resistance in future; nevertheless, everything changed in 2016 with a bold move. The Ministry of Health and Medical Education (MOHME) set up and published a “national action plan of Islamic Republic of Iran to combating antimicrobial resistance (IRIAMR)” to stop and reverse the trend. In spite of MOHME efforts, after two years of implementing the program, there has been no tangible change in the control and deceleration of antimicrobial resistance in Iran’s hospitals in recent field studies. We believe that the effect of comprehensive IRIAMR guideline has been reduced by the important weak points including:  I) Poor coordination between different departments of the MOHME, Iran veterinary organization and Iran health insurance organization, II) Not taking IRIAMR guideline serious by hospitals, networks and health centers, and staff at health centers, III) Using various methods for antibiotic sensitivity testing, IV) Serious weaknesses in controlling of hospital laboratories to perform tests in a standard manner, V) Not operationalizing guidelines designed for the classification of antibiotic use in health care centers and hospitals and etc. At last, despite all the inconveniences involved in the implementation of this program, if the weaknesses were resolved, it would be expected that by the year 2021, Iran would be among the pioneer and the successful countries in controlling antibiotic resistance.