Chronic, non-infectious diarrhea can be caused by a variety of gastrointestinal diseases. In anamnesis, it is important to take accompanying warning symptoms and specific triggers into account. The fecal inflammatory marker calprotectin may help differentiating between organic and functional gastrointestinal disorders, but it is not specific. Among other options, gelling fibres, Loperamide and Cholestyramine as well as probiotics are available for the symptomatic treatment of chronic diarrhea. For long-term treatment of chronic diarrhea with the enkephalinase inhibitor racecadotril, which is approved for acute diarrhea, only limited data are available. Eluxadolin presents a new therapeutic option. It can alleviate abdominal pain and diarrhea by modulation of opioid receptors in the enteric nervous system. Additional approaches in intractable irritable bowel syndrome with diarrhea (IBS-D) include 5-HT3 receptor antagonists, the antibiotic Rifaximin as well as low-dose tricyclic antidepressants. Specific diets such as the low-FODMAP diet can also relieve symptoms in IBS.