Immunization against many vaccine preventable diseases (VPD) is highly cost-effective, in terms of both direct morbidity and mortality prevented [1] and broader indirect macroeconomic impact [2]. Considerable resources have been devoted, therefore, towards procurement and delivery of existing vaccines (e.g., measles, polio, rotavirus, HPV) [3], development of new vaccines against other known (e.g., malaria, HIV, cervical cancer), and emerging (e.g., COVID-19, Ebola, Zika) pathogens in resource-limited countries (RLCs) and beyond [4, 5]. The decision to immunize a specific individual against a specific VPD, like other medical interventions, ideally requires a careful weighing of risks and benefits. While vaccines have a clinically acceptable safety profile and are generally well tolerated, vaccine-related safety issues can occur either during clinical trials or afterwards at any point during the process from manufacturing to the administration of such vaccines in the “real-world.” Therefore, in RLCs, the potential immunization risks expand beyond adverse events following immunizations (AEFI) from the specific vaccine preparation (e.g., anaphylaxis) to those due to poor immunization programme practices such as unsafe injection practices, like reuse of syringe and needles contaminated with pathogens [6, 7], unsafe storage/reconstitution of vaccine [8], unsafe medical waste disposal [9], and overall poor programme monitoring and evaluation [10]. Effective surveillance for AEFIs in RLCs should ideally include this broader scope of immunization risks to enable their eventual control and elimination when possible. This chapter is focusing on pharmacovigilance and pharmacoepidemiological aspects of AEFIs with a focus on RLCs.