The clinical presentation and epidemiology of infective endocarditis (IE) have evolved over time. While the cornerstones of IE treatment remain antimicrobial therapy and surgery, percutaneous mechanical aspiration (PMA) has emerged as an option for carefully selected patients as a complementary modality, based on retrospective data, case series, and expert experience. In this comprehensive review, we summarize the proceedings from an inaugural summit dedicated to the discussion of PMA in the global management of IE, consisting of experts across multiple disciplines from diverse geographic regions and care environments. After conceptualizing the 3 major roles of PMA as a bridge to decision, destination therapy, and adjunctive therapy, we then review the clinical scenarios in which PMA might be considered by IE subtype. We discuss patient selection, the rationale for intervention, and the most recent evidence for each. Next, we consider PMA for IE in the larger context of our health care system across 3 domains: clinical collaboration, financial considerations, and academic innovation, emphasizing the importance of interdisciplinary teams and cross-organizational partnerships, reimbursement models, and the need for high-quality research. Finally, we outline what we determined to be the most pressing outstanding questions in this space. In doing so, we propose a national consortium to help organize efforts to move this field forward and share our progress in these endeavors to date. PMA for IE has great promise, but significant work remains if we are to fully realize its potential to safely and effectively improve outcomes for modern endocarditis patients.