Helicobacter pylori eradication strategies continue to adapt in response to increasing antimicrobial resistance. Among traditional regimens, bismuth-based quadruple therapy remains the most consistently effective first-line treatment, with registry data and randomized trials demonstrating eradication rates of over 90%, particularly when delivered as a single-capsule formulation. Clarithromycin-based triple therapy remains viable in select cases with confirmed susceptibility but underperforms in empirical use. The emergence of potassium-competitive acid blockers, notably vonoprazan, offers a compelling alternative to proton pump inhibitors, showing high efficacy when combined with dual, triple and quadruple regimens. These combinations frequently demonstrate non-inferiority to longer or more complex therapies. Adjunctive probiotic use continues to improve treatment tolerability and microbiota recovery. Overall, bismuth-based quadruple therapy and potassium-competitive acid blocker-containing regimens represent the most robust empiric options, with regional resistance patterns and tailored approaches remaining critical to optimizing patient outcomes.