This conversation examines a major Canadian cohort study evaluating whether periprosthetic joint infection after primary arthroplasty independently increases long-term mortality. The investigators describe a clear signal: although infection remains rare, patients who develop one within a year face markedly elevated 10-year mortality, even after robust matching for comorbidities using validated provincial datasets. They highlight the biological plausibility—underlying immune and metabolic vulnerabilities likely drive colonization toward full infection—and emphasize that swift diagnosis and effective management may mitigate risk. Looking ahead, they call for advances in prevention, timely treatment, and potential centralization to high-volume or infection-focused surgeons, noting that even rare outcomes warrant coordinated global effort when consequences are profound.