Despite the large number of suggestions available in the literature, the optimal duration of antibiotic treatment remains an individual decision mainly based on clinical criteria. Shorter but equally effective regimens would reduce the side effect rates, including both antibiotic resistance and drug expenses. Although several prospective, randomized trials and meta-analyses with the aim of comparing a standard duration with a shorter one for most bacterial infections have been published, to date most current recommendations carry little weight, as they are based on expert opinions or practical experience. This review will briefly touch upon the clinical evidence of short-course versus long-course antibiotic therapy for the most common community- and hospital-acquired bacterial infections.