Despite levels of health spending that are higher per capita and as share of gross domestic product than any country worldwide, the US health care system is fragmented, technology and administration heavy, and primary care deficient. Studies of regional variations in US health care show similar "disconnects" between higher spending and better health outcomes. Faced with rising health benefit costs and suboptimal workforce health amid economic downturn, concerned US employers have implemented innovative payment and health care delivery strategies such as consumer-driven health plans and targeted prevention programs. The former may impose undue cost shifting, prohibitive out-of-pocket expenses, and health literacy challenges, while the latter have shown inconsistent near-term economic returns and long-term clinical efficacy. Employers have begun exploring more comprehensive health delivery platforms such as integrated worksite primary care clinics that have potential to cost-effectively address several pressing problems with current US health care: the growing primary care physician shortage, poor access to routine care, lack of coordinated and patient-centered treatment models, low rates of childhood immunizations, and "quality-blind" fee-for-service payment mechanisms. Such on-site medical clinics exploit one of the rare comparative strengths of the US health care system-its plentiful supply of highly skilled registered nurses-to offer workers and their dependents convenient, high-quality, affordable care. A relatively recent health care paradigm, worksite clinics must yet develop consistent reporting strategies and credible demonstration of outcomes. This review explores available evidence regarding worksite primary care clinics, including current rationale, historical trends, prevalence and projected growth, expected health and financial benefits, challenges, and future research directions.