<b><i>Background:</i></b> Dyspepsia is one of the most common complaints in gastroenterology. While its etiology is usually benign, rare cases of malignancy have to be identified. Individualized risk stratification is essential for cost-effective management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia at the specialist level and provide a framework for rational workup and surveillance strategies. <b><i>Summary:</i></b> Causes of dyspepsia can be functional or organic, including gastritis, peptic ulcers, or malignancy. <i>H. pylori</i> gastritis represents a specific entity of dyspepsia and increases the risk of gastric cancer. <i>H. pylori</i> eradication can improve symptoms in a subset of patients and reduce gastric cancer risk. In young patients without alarm features, malignancy is rare, and noninvasive testing for <i>H. pylori</i> is appropriate. In elder patients and those with alarm features, high-quality endoscopy is the method of choice to rule out malignancy. Advanced corpus-predominant atrophic gastritis with or without intestinal metaplasia represent precancerous lesions. <b><i>Key Messages:</i></b> Symptom assessment requires to distinguish dyspepsia of functional or organic origin. Risk stratification in dyspeptic patients is based on age, alarm features, and <i>H. pylori</i> status. Noninvasive test-and-treat is recommended in patients with low gastric cancer risk, while endoscopy is recommended in individuals at increased risk. <i>H. pylori</i> infection should be eradicated in order to obtain a symptomatic benefit and reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic surveillance.