Infectious diseases are conditions with significant consequences in terms of public health while associated mortality, morbidity, and complications can be prevented. Disease severity and duration can be shortened by means of rational antimicrobial therapy. It is important to obey main rational antibiotic use rules ie. to collect and examine appropriate culture specimens before treatment, identify potential microbial agents, consider the pharmacological properties of the antibiotic, determine whether combined antibiotics are indicated, review the host factors and indications for antibiotic therapy modification, and monitor response to antibiotic therapy while planning antibiotic therapy. Once correct diagnosis has been made, the correct antibiotic must be administered via the correct route, at an effective dose, at optimum intervals, and for an appropriate length of time for rational antimicrobial therapy. However, knowledge concerning the optimal duration of treatment is limited. Patients generally receive antibiotic therapy for 10-14 days. Prolonged treatment is also common. Duration of antimicrobial therapy may be a confusing issue for clinicians due to problems of resistance and toxicity. A healthy bacterial ecosystem (i.e. a normal flora) is essential to remain healthy. Antibiotic use can alter the normal bacterial flora in humans, which generally leads to the emergence of multidrug-resistant (MDR) bacteria and side effects such as diarrhea. Infections caused by MDR bacteria result in increased disease and mortality rates and extended hospital stays, as well as increased costs. Studies aimed at shortening the duration of treatment have reported that a 3-5 day treatment period in some of the community-acquired infections and one-week period in some of the nosocomial infections may be sufficient. Based on the patients' individual characteristics and clinical responses to treatment, short-term antibiotic therapy may be administered in selected patient groups both in community-acquired and healthcare-associated infections. Rational antibiotic therapy, together with observation of response to treatment and optimal treatment durations (which remain to be determined) can prevent adverse outcomes associated with long-term antibiotic use such as antibiotic-related side effects and development of MDR bacteria.