Acute respiratory infections (ARIs) are a major cause of morbidity and mortality across the life span. Globally, an estimated 17 billion ARIs occur each year, accounting for 2.4 million deaths (>740,000 deaths among children). Although the majority of these ARIs are caused by respiratory viruses, most severe or fatal cases are caused by bacterial respiratory pathobionts. Increasingly, commensal microbes in the upper respiratory tract (URT) are recognized to influence the risk and severity of respiratory viral infections and resistance to colonization and infection by bacterial pathobionts. Consequently, there is growing interest in leveraging these microbe–microbe or microbe–host interactions to develop novel strategies for ARI prevention or treatment. Although the modern history of probiotics dates back more than a century, intranasal administration of live bacterial strains would represent a shift in our approach to preventing and treating ARIs. Necessary characteristics of such nasal probiotics would include the ability to adhere to the epithelium and successfully colonize the human URT, a lack of cytotoxicity to respiratory epithelial cells, some degree of resistance to horizontal gene transfer and mobile genetic elements, a low propensity to invade host tissues, and susceptibility to commonly available antibiotics. Below, we describe an understudied bacterial species, Dolosigranulum pigrum, which is increasingly viewed as a keystone species within the human URT and a promising nasal probiotic candidate for ARI prevention or treatment.