Pakistan’s Expanded Programme on Immunization (EPI) performance has a significant impact on global and regional immunization indicators such as poliomyelitis eradication, maternal and neonatal tetanus and measles elimination. Despite significant efforts by the Government and partners, Pakistan’s immunization indicators have not met the expected benchmarks. Barriers to achieving immunization goals are related to limited access to immunization services, lack of parent awareness and weak management. With sustained Government commitment, predictable partner support and by adopting effective strategies, Pakistan can achieve the immunization targets set at the regional and global level and make strong progress towards achieving Millennium Development Goal 4. This paper reviews EPI coverage targets, constraints, costs and resource allocation, and financial impact of suboptimal performance, and indicates the way forward to overcome these challenges.