Abstract Antibiotic resistance has resulted in unsatisfactory eradication results with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates. Sequential therapy with amoxicillin (1 g twice a day) and a proton pump inhibitor (PPI) (twice a day) given for 5 days followed by a PPI plus clarithromycin (500 mg twice a day) and tinidazole (500 mg twice a day) for 5 days is now a first‐line therapy for Helicobacter pylori in some countries. Standard triple therapy is effective in regions where clarithromycin resistance is low. Levofloxacin based triple therapy is an effective alternative to quadruple therapy in second‐line treatment. Adjuvant therapy may reduce side‐effects and improve compliance. Molecular and genomic research on H. pylori may result in the development of targeted antibiotic therapy; however, more research is required in this field. Further research in vaccination is also necessary before this can become an option in clinical practice.