Climate change and variability present new challenges for agriculture, particularly for smallholder farmers who continue to be the mainstay of food production in developing countries. Recent global food crises have exposed the structural vulnerability of globalized agri-food systems, highlighting climate change as just one of a complex set of environmental, demographic, social and economic drivers generating instability and food insecurity, the impacts of which disproportionately affect poorer groups in marginal environments. Rather than search for single causes, there is a need to understand these changes at a systemic level. Improved understanding of and engagement with the adaptive strategies and innovations of communities living in conditions of rapid change provides an appropriate starting point for those seeking to shape agricultural innovation systems responsive to food insecurity and climate change. This paper draws lessons from selected country experiences of adaptation and innovation in pursuit of food security goals. It reviews three cases of systems of innovation operating in contrasting regional, socio-economic and agro-ecological contexts, in terms of four features of innovation systems more likely to build, sustain or enhance food security in situations of rapid change: (i) recognition of the multifunctionality of agriculture and opportunities to realize multiple benefits; (ii) access to diversity as the basis for flexibility and resilience; (iii) concern for enhancing capacity of decision makers at all levels; and (iv) continuity of effort aimed at securing the well-being of those who depend on agriculture. Finally, implications for policymakers and other stakeholders in agricultural innovation systems are presented.