Vaccines have non-specific effects (NSE) on subsequent morbidity and mortality from non-vaccine related infectious diseases. Thus NSE refers to any effect that cannot be accounted for by the induction of immunity against the vaccine-targeted disease. These effects are sex-differential, generally being more pronounced in females than males. Furthermore, the NSE are substantial causing greater than fifty percent changes in all cause mortality in certain settings, yet have never been systematically tested despite the fact that millions of children receive vaccines each year. As we strive to eliminate infectious diseases through vaccination programmes, the relative impact of NSE of vaccines on mortality is likely to increase, raising important questions regarding the future of certain vaccine schedules. A diverse group of scientists met in Copenhagen to discuss non-specific and sex-differential effects of vaccination, and explore plausible biological explanations. Herein we describe the contents of the meeting and the establishment of the 'Optimmunize' network aimed at raising awareness of this important issue among the wider scientific community.