The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome.