There is a global crisis of antibiotic resistance in part because of the collateral damage of antibiotic use. Reduction in antibiotic consumption is clearly important to minimize this problem. Limiting treatment duration may be the most clinically palatable means of reducing antibiotic consumption. Antimicrobial stewardship programs play an important role in this process. Their effectiveness may be increased by drawing on evidence from randomized controlled trials regarding optimal antibiotic duration. However, in most clinical scenarios, the recommended duration of therapy in published guidelines is based on expert opinion. Biological markers, such as procalcitonin, have been shown to reduce antimicrobial consumption with no adverse outcome in 11 randomized controlled trials. Although procalcitonin may not be the perfect biomarker, the concept of procalcitonin-guided antibiotic discontinuation after clinical stabilization, in conjunction with antimicrobial stewardship programs, appears to be ready for introduction into clinical practice.