Helicobacter pylori(H. pylori) is a key agent in several upper gastrointestinal diseases. Treatment ofH. pyloriinfection is the main strategy for resolving the associated gastroduodenal damage in infected patients and for the prevention of gastric cancer development. Infection management is becoming complex due to the increase in antibiotic resistance, which already represents a global healthcare problem. Resistance to clarithromycin, levofloxacin or metronidazole have forced the adaptation of eradication regimens in this new reality to reach the eradication rate target recommended in most international guidelines (>90%). In this challenging scenario, molecular methods are revolutionizing the diagnosis of antibiotic-resistant infections and the detection of antibiotic resistance and opening a path towards personalized treatments, although their use is not yet widespread. Moreover, the infection management by physicians is still not adequate, which contributes to aggravating the problem. Both gastroenterologists and mainly primary care physicians (PCPs), who currently routinely manage this infection, perform suboptimal management of the diagnosis and treatment ofH. pyloriinfection by not following the current consensus recommendations. In order to improveH. pyloriinfection management and to increase PCPs’ compliance with guidelines, some strategies have been evaluated with satisfactory results, but it is still necessary to design and evaluate new different approaches.