Research into the human microbiome will substantially enhance our understanding of inflammatory, metabolic and malignant diseases. The complexity of this research area can only be addressed by an interdisciplinary translational approach including bioinformatics. Data derived from pure in silico analyses and statistical associations will not automatically translate into sound clinical concepts, as we have learned previously in genetics. Potential targets for future treatment strategies include the proven impact of nutrition and medication on microbial diversity and therapeutic effects of microbial metabolic processes and metabolites. Fecal microbial transplantation (FMT) beyond its indication in refractory Clostridium difficile infection (CDI) should be held against the same standards and regulated by the same procedures that are applied to all investigational compounds and treatments prior to their approval. Donor fidelity, sample processing and recipient safety (including the role of fecal pathogens and toxins) need thorough scientific investigation and evaluation in clinical trials with objective outcome parameters prior to any recommendations for clinical practice.