In the last decade, the controversy of sphincter of Oddi dysfunction (SOD) as a clinical entity has abated. The challenges facing clinicians caring for patients with suspected SOD are to effectively and safely diagnose and treat these patients. Sphincter of Oddi (SO) manometry (SOM) remains the gold standard for the diagnosis of SO dysfunction SOD. Several non-invasive screening tests for patients with pancreaticobiliary pain have been developed because SOM is associated with significant complications. Ultrasonography is useful for screening of organic pancreaticobiliary diseases but not for functional ones. Although magnetic resonance cholangiopancreatography (MRCP) is a safe, noninvasive method of examining the pancreaticobiliary tree abnormalities, it may currently have limited use in patients with suspected SOD. Quantitative hepatobiliary scintigraphy (QHBS) appears to become a promising method for identification of patients with biliary type SOD, and it should be employed prior to invasive diagnostic tests. ERCP for patients with type III SOD must be coupled with diagnostic SOM of both biliary and pancreatic sphincters since there are a high concordance of dual sphincter dysfunction. SOM is currently the gold standard of choice for evaluating SOD is the best predictor of outcome from sphincter ablation in type II and type III patients regardless of whether there is pancreatic or biliary SOD. In pancreatic SOD patients, biliary sphincterotomy alone may be inadequate for a treatment for some pancreatic type II patients. Medical therapy for SOD using smooth muscle relaxants has been disappointing and surgical therapy may play a role in limited number of cases that failed endoscopic therapy. Endoscopic intrasphincteric injection of Botulinum toxin is effective in patients with SOD and has minimal risks but it provides short-term efficacy. It may play a role as a first line diagnostic challenge, predicting which patient may ultimately respond to endoscopic sphincterotomy.