Diffuse esophageal spasm (DES) is a rare motility disorder characterized by irregular smooth muscle contractions in the esophagus, leading to dysphagia, chest pain, and regurgitation. Despite its significant impact on quality of life, the etiology of DES remains unclear, with theories suggesting disruptions in peristalsis coordination, muscular hypertrophy, or nerve dysfunction. Recent advances in diagnostic techniques, particularly high-resolution manometry (HRM) and the functional lumen imaging probe (FLIP), have enhanced the accuracy of diagnosing DES. The chapter discusses the clinical presentation of DES, emphasizing the episodic nature of symptoms and the need for specialized testing to rule out other conditions. Treatment options focus on symptom management rather than addressing the underlying causes. Pharmacologic therapies, including proton-pump inhibitors, smooth muscle relaxants, and peppermint oil, have shown variable efficacy. Treatments like botulinum toxin injections and peroral endoscopic myotomy (POEM) are considered for refractory cases, though their long-term effectiveness in non-achalasia disorders is still debated. Overall, the chapter underscores the complexity of DES, highlighting the urgent need for further research to better understand its mechanisms and optimize treatment strategies.