Both asthma and rhinosinusitis are complex and heterogeneous diseases and, importantly, they often coexist: these diseases can be concomitant in 35–65% of affected children, according to different studies. Thus, evaluating this comorbidity in the clinical practice should be paramount. In this review, we focused our discussion on the multiple pathophysiological aspects that may link rhinosinusitis and asthma in the pediatric population. Although rhinosinusitis may exacerbate asthma through several mechanisms occurring by contiguity, actually this aspect seems to be only one component of the complex interplay between upper and lower airways. In particular, the onset of an important and persistent Th2-driven inflammatory process dominated by eosinophils presence at one site of the airways, may release into the bloodstream several cytokines; in their turn, those can lead to the stimulation of the bone marrow, which may function as a systemic amplifier of such an eosinophilic inflammation.