There has been an exponential rise in research into the microbiota of the human gastrointestinal tract, particularly of the genomic content (the microbiome). The vast number of micro-organisms residing in our gut has an integral role in essential processes, including growth and development. Probiotics, live micro-organisms with putative benefits on health have become ubiquitous as treatments for many conditions, despite often limited robust clinical trial data. However, the resurgence of faecal microbial transplantation as an effective treatment modality provides further promise that manipulation of our microbiome can have clinical benefits. This review will present the recent evidence for the role of the microbiome in development and growth, and focus on the evidence for its manipulation in paediatric diseases. We will show that while there is promising data in specific diseases, there remain many unanswered questions. Only through a deeper understanding of our complex internal ecosystem will we be able to move to the next stage of targeted microbial therapy.