Vaccine “hesitancy” is an emerging term in the literature and discourse on vaccine decision-making and determinants of vaccine acceptance. It recognizes a continuum between the domains of vaccine acceptance and vaccine refusal and de-polarizes previous characterization of individuals and groups as either anti-vaccine or pro-vaccine. The primary aims of this systematic review are to: 1) identify research on vaccine hesitancy; 2) identify determinants of vaccine hesitancy in different settings including its context-specific causes, its expression and its impact; and 3) inform the development of a model for assessing determinants of vaccine hesitancy in different settings as proposed by the Strategic Advisory Group of Experts Working Group (SAGE WG) for dealing with vaccine hesitancy. A broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy around vaccines, was applied across multiple databases. Peer-reviewed studies were selected for inclusion if they focused on childhood vaccines [≤7 years of age], used multivariate analyses, and were published between January 2007 and November 2012. Our results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence. Determinants of vaccine hesitancy are complex and context-specific – varying across time, place and vaccines.