For reasons of antibiotic resistance and side effects, macrolides should be prescribed with care in the pediatric population. We evaluated the adherence to Dutch guidelines of macrolide prescription in children and estimated the risk of Mycoplasma pneumoniae–associated pneumonia based on Fischer’s decision tree. In this retrospective study, we included children aged 0–18 years who were treated with azithromycin or clarithromycin for pulmonary disease in four settings from general practice to hospital ward for (1) the prescriptions not in accordance with the guideline of the Dutch Association of Pediatrics and (2) the risk of M. pneumoniae in patients with community-acquired pneumonia (CAP) according to Fischer’s decision tree. The latter suggests that children older than three years with a fever lasting more than two days are at high risk for M. pneumoniae and that it is therefore justified to treat them with macrolides. In total, 189 macrolide prescriptions from 2015 until 2017 were analyzed: 139 children used macrolides for a pulmonary indication (75%); 18% (n = 25) of the prescriptions were not in accordance with Dutch guidelines. Only 9.1% of patients with CAP were classified as having a high risk of M. pneumoniae according to Fischer’s decision tree. A significant proportion of macrolide prescriptions for Dutch children with a pulmonary disease appears not to be in accordance with the guidelines. Most patients with CAP treated with a macrolide actually had a low risk of having M. pneumoniae according to Fischer’s decision tree. Both observations suggest overuse of macrolides in children.