School nurses often have the responsibility to ensure that students meet all immunization requirements for school entry and school attendance. In large inner-city school districts, many obstacles exist which make this task daunting and often result in lengthy absences and exclusions for students. It is critical that school nurses find creative and systematic ways to meet these challenges, which include working parents, lack of access to primary care, lack of transportation, cost of immunizations, poor compliance and follow-up, myths regarding immunizations, and the impact of the Health Insurance Portability and Accountability Act (HIPAA) legislation. This article describes an immunization project that removed most of those barriers for high-risk students and gave the school nurses tools to succeed in achieving higher levels of immunization compliance in inner-city schools. Since the immunization project's conception, compliance in the district has risen from an overall level of 50-60% to 90-100%, along with better record-keeping and the prevention of exclusions. (Contains 2 tables.)