Antibiotic era was started with the great discovery of penicillin which influenced the existence of humanity. Many novel antibiotics were discovered during the year 1950 to 1960, termed as golden era for antibiotics. Soon after the discovery of several antibiotics, antimicrobial resistance had started emerging. With emerging resistance and non-availability of new antibiotics we are heading towards post antibiotic era. As antimicrobial resistance is becoming a global public health threat, we need an alternative therapy to protect human health. To combat this situation, we need to focus on where antimicrobial resistance originated and the factors associated with its spread. In this review, we have highlighted the history behind origin of antimicrobial resistance, its evolution timeline, drivers of antimicrobial resistance, mechanism of resistance developed and alternative approaches and interventions to combat with this situation keeping an eye on the Indian scenario as well.