Immune memory was for a long time thought to be an exclusive feature of the adaptive immune system. Emerging evidence has shown that the innate immune system may exhibit memory which has been termed as trained immunity or innate immune memory. Trained immunity following vaccination may produce non-specific effects leading to reduction in morbidity and mortality from heterologous pathogens. This review looked at trained immunity as a mechanism for vaccine induced non-specific effects, mechanisms underlying trained immunity and known vaccine non-specific effects. A discussion is also made on the implications these vaccine non-specific effects may have on overall risk-benefit ratio evaluation by National Medicines Regulatory Authorities (NMRAs) during licensure of new vaccines. Epigenetic remodeling and "rewiring" of cellular metabolism in the innate immune cells especially monocytes, macrophages, and Natural Killer (NK) cells have been suggested to be the mechanisms underlying trained immunity. Trained immunity in other innate cells has largely remained elusive up to date. Non-specific effects have been extensively documented with Bacille Calmette-Guerin (BCG), measles vaccine and oral polio vaccine but it remains unclear if other vaccines may exhibit similar effects. All known vaccine non-specific effects have come from observations in epidemiological studies conducted post-vaccine licensure and roll out in target populations. It remains to be seen if early identification of non-specific effects especially those with protective benefits during the clinical development of new vaccines may contribute to the overall risk-benefit ratio evaluation during licensure by NMRAs.