Antibiotic resistance is one of the main challenges of the new century which has limited the use and effectiveness of many first-line antibiotics. The excessive and irrational use of antibiotics has assisted the microbes to modify their genes and metabolic activities, thereby developing resistance. Addressing the situation in developing countries in Southeast Asia region, poor hygiene, lack of sanitation, and inequalities in treatment access have further increased the infectious disease burden. In over a decade, the high prevalence rate of infections and resistant to antibacterials has appeared to be a big challenge. In addition, poor compliance to antibacterial use protocols and excessive use of antibacterials has minimized the therapeutic effectiveness of these drugs. A huge challenge in Southeast Asian setting is the resistance among majority of bacteria responsible for sexually transmitted diseases which is still largely unknown. It is the paramount responsibility of local health authorities to effectively conserve the efficacy of existing antibacterials while decreasing emergence and transmission of resistance.