The gastrointestinal microbiota is a complex ecosystem with each human individual hosting at least 160 different bacterial strains. Our understanding of its role is rapidly expanding as a result of the molecular microbiological techniques that can accurately characterise its composition and 'omics' technologies that measure its metabolic activity. Since 1995, extensive research has investigated the prebiotic concept, which describes how supplementation of some non-digestible oligosaccharides can stimulate the growth and/or activity of specific genera including bifidobacteria. However, the vast majority of studies are in healthy human subjects, with few undertaken in patients with disorders relevant to clinical nutrition. Marked alterations of the luminal microbiota have been demonstrated in patients with digestive disorders, highlighting mechanisms through which they might be involved in their pathogenesis, including higher clostridia in patients who develop diarrhoea during enteral nutrition and the influence of bifidobacteria on intestinal dendritic cell phenotype in Crohn's disease. The impact of prebiotics on the intestinal microbiota of healthy people has not been consistently replicated in patients with digestive disorders. For example, a number of studies show that inulin/oligofructose do not increase bifidobacteria in enteral nutrition and Crohn's disease. Indeed, in Crohn's disease and irritable bowel syndrome there is evidence that some prebiotics in high doses worsen functional symptoms. Unlike healthy human subjects, patients experience a number of issues that may alter their gastrointestinal microbiota (disease, antibiotics and inflammation) and the use of microbiota modifying therapies, such as prebiotics, do not always elicit the same effects in patients as they do in healthy people.