Introduction: The majority of acute respiratory tract infections (RTIs) are caused by viruses and the overzealous use of antibacterial drugs, when not really required, is a cause for concern. This has led to evaluation of alternative approaches such as boosting the immune response in individuals who are most vulnerable to develop RTIs such as the very young and the elderly. Areas covered: This article overviews the immunostimulant activity and pharmacokinetic properties of pidotimod, and focuses on assessing its role in the treatment and prevention of acute RTIs through evaluation of clinical trials and real-world evidence. Articles were obtained from a full search of Medline, and this was augmented by published clinical studies known to the authors and manufacturer. Expert opinion: Pidotimod's activity was shown to be mediated via multiple pathways of the immune system. Comparison with placebo demonstrated significant advantages for pidotimod in terms of reduced reinfection rates [OR 0.20, 95% CI 0.12 to 0.33; p < 0.00001], a lesser need for antibiotics [mean difference -2.65, 95% CI -3.68 to -1.62; p < 0.00001] and rescue medications, and decreased absenteeism [mean difference-2.99, 95% CI -4.03 to -1.95; p < 0.00001]. No safety concerns were raised in these studies.