Despite doctors' expectations, non-compliance is common in short-term antibiotic therapy of respiratory tract infections (RTIs). This phenomenon has profound practical implications. It leads to ineffective management, the deterioration of patients' health, hospital admissions, additional costs and the emergence of antibiotic-resistant microorganisms. This article reviews methods of measuring compliance with antibiotics in the outpatient-based management of RTIs and research results. Causes of non-compliance are also discussed. Factors influencing compliance are analysed, as well as practical strategies for addressing non-compliance with antibiotic therapies for RTIs. The influence of the frequency of doses on compliance is particularly stressed, as it has been observed that once daily dosing has almost a 100% compliance rate. As a number of once-daily antibiotic preparations are available now, the possibility of using once-daily schedules for improving compliance in RTI cases is stressed.