Several studies have shown wide variations in the delivery of hospital-based care to patients with acute ischemic stroke. The findings of these studies suggest that recommendations drawn from published evidence-based or consensus-based guidelines are implemented inconsistently. Although rates of adherence to stroke quality indicators can be increased through the use of targeted quality improvement (QI) efforts, stroke QI programs are still in their infancy. Current stroke QI programs are often highly variable and poorly coordinated, rely on differing definitions of key data elements and/or indicators, and are challenging to implement and sustain in resource-constrained healthcare environments. Key barriers to long-term success of these programs include inadequate funding at the local and national level, lack of infrastructure to support electronic data capture for QI as part of the process of patient care, lack of a single clearinghouse for uniform data definitions and performance indicator descriptions, competing survey instruments to monitor hospitalized stroke care, and constraints on inpatient and post-discharge data collection imposed by the new Federal Health Insurance Portability and Accountability Act Privacy Rule. In addition, the competing needs of registry activities (e.g., complete case ascertainment) versus QI efforts (e.g., incremental tests of change) must be balanced. Potential solutions include: (1) financial incentives to healthcare providers and institutions for participation in QI initiatives; (2) financial incentives to healthcare providers and institutions for measurable improvements in care; (3) mandatory data reporting on key measures of stroke care; and (4) promotion of active and sustainable collaborations among key stakeholders including healthcare providers (e.g., physicians, nurses), healthcare organizations (e.g., hospitals, physicians' groups), quality improvement organizations, health payers and insurers, public health departments, and state and federal health agencies to create a single national stroke registry for stroke QI.