The “human super-organism” refers to the human body and the massive numbers of microbes which dwell within us and on the skin surface. Despite the large numbers of microbes co-existing within the human body, humans including infants and children achieve a physiologic state of equilibrium known as health in the context of this microbial world. These key concepts suggest that many individual members of the human microbiome, including bacterial and fungal species, confer different benefits on the human host. Probiotics, or beneficial microbes, may modulate immune responses, provide key nutrients, or suppress the proliferation and virulence of infectious agents. The human microbiome is in fact dynamic and often in flux, which may be indicative of the continuous interplay among commensal microbes, pathogens, and the human host. In this article we review the state-of-the-art regarding probiotics applications to prevent or treat diseases of the pediatric gastrointestinal and genitourinary systems. Additionally, probiotics may regulate local and systemic immunity, thereby reducing allergic disease severity and susceptibilities of infants and children to allergies and atopic diseases. In summary, beneficial microbes offer promising alternatives for new strategies in therapeutic microbiology with implications for different subspecialties within pediatrics. Instead of simply trying to counteract microbes with vaccines and antibiotics, a new field of medical microbiology is emerging that strives to translate human microbiome research into new probiotics strategies for promotion of health and prevention of disease in children.