Musculoskeletal infections are a leading cause of patient morbidity and rising healthcare expenditures. The incidence of musculoskeletal infections, including soft-tissue infections, periprosthetic joint infection, and osteomyelitis, is increasing. Cases involving both drug-resistant bacterial strains and periprosthetic joint infection in total hip and total knee arthroplasty are particularly costly and represent a growing economic burden for the American healthcare system. With the institution of the Affordable Care Act, there has been an increasing drive in the United States toward rewarding healthcare organizations for their quality of care, bundling episodes of care, and capitating approaches to managing populations. In current reimbursement models, complications following the index event, including infection, are not typically reimbursed, placing the burden of caring for infections on the physician, hospital, or accountable care organization. Without the ability to risk-stratify patient outcomes based on patient comorbidities that are associated with a higher incidence of musculoskeletal infection, healthcare organizations are disincentivized to care for moderate- to high-risk patients. Reducing the cost of treating musculoskeletal infection also depends on incentivizing innovations in infection prevention.