Octreotide analogs are used in the treatment of neuroendocrine tumors and are investigated as treatment options in many diseases. These agents mimic somatostatin effect which is inhibitory to pancreatic hormones. The most common side effects are biliary dysfunction and gastroenterologic disorders. Pancreatic insufficiency is a common adverse effect of this medication which is explained by the direct inhibition of pancreatic hormones responsible for stimulating the production and excretion of pancreatic enzymes. This side effect is misdiagnosed leading to increasing octreotide analog dosage, and eventually more pancreatic insufficiency and cost of treatment. We report our experience with pancreatic insufficiency developing in neuroendocrine tumor patients treated with octreotide analogs, reviewing the pathogenesis of this side effect. This common but underpublished condition is easy to diagnose and treat.