Pidotimod is a synthetic dipeptide that exerts immunomodulatory activity, modifying innate and adaptive immunity. Pidotimod firstly acts on Toll-like receptors, then on antigen-presenting cells and other immunocompetent cells. Pidotimod also affects immunoglobulin production and their switching. Evidence shows that pidotimod effectively and safely prevents respiratory infections, mainly in children with recurrent and frequent infectious episodes. In addition, pidotimod may be helpful as an add-on strategy in managing children with infections. Finally, there is evidence that pidotimod, thanks to its immunomodulatory activity and preventing respiratory infections (the main trigger for asthma exacerbation), may be beneficial in managing subjects with asthma and allergic diseases. The present review presents and discusses the most recent studies conducted in children with asthma, allergic rhinitis, recurrent respiratory infections and acute infections. Lastly, pidotimod is safe and well-tolerated in children.