The role of healthy volunteers (HV) in research covers a wide spectrum. In gastrointestinal research HV are often considered a control population. Endoscopy-based investigations are rare in terms of all studies performed in this field. The term ‘healthy’ must be questioned in some cases, as Helicobacter pylori- positive individuals are included as well. Problems arise from several fields, e.g. safety, financial compensation, incomplete ethical votes, lack of documentation, lack of defining limitations, overuse of invasive procedures. This article will discuss these problems in detail and will finally give an overview of key issues for extended ‘good clinical practice’.