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Treatments and diagnostic methods for Helicobacter pylori (H. pylori) infection have evolved in recent years. While it is estimated that 95% of H. pylori infections should respond to guided antibiotic therapy—that is, therapy tailored to the bacterium’s susceptibility to antibiotics as determined by PCR (polymerase chain reaction) and/or culture from gastric biopsies—it is observed that almost all patients still receive empirical treatment, despite recommendations from international and national learned societies and the French National Authority for Health (HAS). Indeed, it has been shown that guided treatments are better tolerated, therefore better adhered to, and thus more effective (better tolerance, better adherence, better efficacy). PCR is a technique capable of detecting H. pylori and the mutations responsible for resistance to clarithromycin, thereby enabling the implementation of guided treatment. It appears to be an alternative to culture, the latter being more difficult to perform. This new approach should allow us to treat nearly 80% of the 200,000 patients diagnosed with H. pylori infection each year with guided triple therapy: a proton pump inhibitor (PPI), amoxicillin, and clarithromycin, instead of the much less well-tolerated empirical quadruple therapy. Indeed, primary resistance to clarithromycin reaches 21% in France. The remaining 20% (patients for whom PCR detects clarithromycin resistance) can be treated with bismuth-based quadruple therapy. With the recent reimbursement of PCR tests, we no longer have any obstacles to implementing this guided therapy, which generates less resistance. Furthermore, few of these treatments have taken into account pharmacokinetic/pharmacodynamic data to adjust dosages and combinations, as is the case for amoxicillin, for which three doses per day are the standard. The indications and sampling precautions remain the same, namely, strict adherence to the discontinuation of PPIs and antibiotics, respectively 2 and 4 weeks before sampling.The GEFH (Groupe d’Études Français des Helicobacter; French Helicobacter Study Group), bringing together hepatogastroenterologists and bacteriologists, has set up a multidisciplinary team meeting to discuss the more or less formal indications for the eradication of H. pylori in the presence of multi-resistance to antibiotics (contactGEFH@helicobacter.fr).