This review provides an overview regarding the main aspects of fatal bacterial infections and antibiotics; in recent years, it has been observed that gram-negative bacteria are prevalent in infections owing to a failure to treat the infection and antibiotic resistance. This has led to the phrase “the end of the antibiotic era,” which was revealed in late 2017. This topic has gained momentum among the journalists, specialists, and broadcasters, who have developed immense interest in exploring new approaches and substitutes for antibiotics to treat infections. Several factors contribute to the increasing antibiotic resistance; these can be divided into two main categories, that is, those caused by human behaviors with respect to antibiotic use and those enacted by pathogens as they attempt to protect themselves against antibiotics. Therefore, the main purpose of this review is to discuss and summarize the most important factors and emphasize the measures to tackle drug resistance worldwide. A comprehensive studies were conducted  to evaluate the reasons of antimicrobial resistance, studying different factors including  bacterial strains (either positive or negative) gram bacteria, antimicrobial agent, in case of  negative  gram bacteria that’s  mean the isolates are not inhibited by the selected antimicrobial agent or by achievable concentrations,  the normal dose schedules and / or the diameters of the area in the range, that’s lead to a specific mechanisms of microbial resistance (e.g., beta-lactamase).