The main purpose of this manuscript is to review the resistance against antibiotics and efflux pumps, one of the mechanisms important in resistance against antibiotics. As a definition, the resistance against antibiotics is accepted as the capability of a microorganism to resist the activity of antimicrobials, which were successfully used to kill the microorganism once. Antibiotic resistance is characterized by several antibiotic susceptibility tests. The wide consumption of antibiotics; the over prescription of antimicrobial drugs by medical doctors; unnecessary, incorrect and inadequate self-medication by the patient and use of several antimicrobial agents either to support a healthy growth or therapeutic purposes in animals consumed as food triggered severe antibiotic resistance. Therefore, the resistance against antimicrobials became a considerable, wide-spread issue in all around the world and the studies have been initiated to overcome the resistance against antibiotics. There are several different mechanisms, which could lead bacteria to be resistant overtime. One of the mechanism of action, which leads to antibiotic resistance, is efflux pumps. Several efflux pump inhibitors were discovered until now, but since some of them are highly cytotoxic, they have very limited use. Understanding efflux pumps and discovering new inhibitors against these pumps could probably save the future of human beings.