Abstract: Antibiotic resistance has always been a hot topic all over the world and its mechanisms are varied and complicated. Our understanding of resistance is ever increasing. On the one hand, physiological and metabolic changes in bacteria can reduce bacterial susceptibility to antibiotics and promote the evolvement of resistance, tolerance and persistence. On the other hand, the regulation of physiological metabolism of bacteria can restore their sensitivity to antibiotics. Recent researches on the relationship between bacterial physiology & metabolism and antibiotic susceptibility were briefly outlined in this paper to provide a better understanding of the mechanism of drug resistance, propose new strategies for clinical treatment and broaden the thoughts on R & D of antibacterial drugs.