In 2010, 7.6 million children under five died, with almost 90% of these deaths attributable to: neonatal causes, pneumonia, diarrhoea, malaria, measles, and HIV/AIDS. Existing immunization programs are estimated to avert between 2-3 million deaths yearly. Of the current child mortality, immunization (including new vaccines against pneumonia and rotavirus) can further prevent approximately 20% of these deaths. This panel describes efforts of multi-agency and government partners at global, regional and country levels to strengthen immunization systems and programs to reduce morbidity and mortality from vaccine-preventable diseases (VPDs), contributing to MDG4. This includes improving equity across target populations, partner coordination, application of the “Reaching Every District” (RED) approach, and examples of best practices and lessons learned to enhance community involvement, service quality and capacity building of health staff at all levels. Immunization programs have successfully reduced VPD incidence and served as a platform for public health interventions and health system strengthening. As a cornerstone towards achieving MDG4, the new Decade of Vaccines global initiative and GAVI Alliance partnership support increasing immunization coverage and worldwide introduction of vaccines against pneumonia, rotavirus, and other priority diseases. Approaches like RED have supported countries to build capacity at sub-national levels (through training, on-the-job improvements, formative supervision, and self-monitoring and assessment) and enable analysis and use of coverage data to improve micro-planning and district/health area prioritization to reach un/under-immunized infants. The Africa Routine Immunization System Essentials (ARISE) project, supported by the Bill & Melinda Gates Foundation, conducted in-depth case studies in 12 districts in three countries (Cameroon, Ethiopia, Ghana), using an assets-based, qualitative methodology plus selected quantitative analyses. Findings indicate that some drivers of improved routine immunization system performance entailed program-specific actions (e.g. interactive, frequent performance review processes), while others pertained to broad health system improvements to strengthen the link between health services and communities. Active community involvement and strong district management emerged as cross-cutting themes essential to moving immunization programs from good to very good levels of performance. In Kenya, the RED approach was implemented (notably in districts in densely populated Nyanza and Western provinces) to reduce the numbers of under-vaccinated children. The focus was on disadvantaged communities, promoting health worker and community partnerships to improve utilization, and improving health worker capacity to continuously use program data to better plan and make informed decisions. Pneumococcal vaccine (PCV) was also introduced into the RI schedule (led by the Ministry of Health with support from partners) and linked with broad efforts to address pneumonia prevention and control in the context of the Global Action Plan for Pneumonia framework. High demand for PCV resulted in many infants returning for vaccination who had previously been “drop-outs”, but this challenged the program’s ability to ensure adequate vaccine supply and meet demand. In 2009, India contributed almost 88% of the 9.8 million children that did not receive DPT3 in the South East Asia Region. At national level and in two of the largest states (Uttar Pradesh and Jharkhand), the RED approach has been adapted to the Indian context by government health staff and NGOs, with a focus on participatory problem identification and solving. Needed immunization tools and job-aids (e.g. on micro-planning, service delivery, cold chain, communication, tracking newborns, etc.) were developed as resources for health staff to improve field level implementation. A key to success has been a capacity building, supportive supervision approach, now known as the “Regular Appraisal of the Program Implementation in District” (RAPID) approach, which empowers local health staff to analyse and address their immunization data and program gaps. As a result of these interventions, Jharkhand’s DPT3 coverage has increased from 29% (1999) to 69% (2009).