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This introduction to the special issue deploys a framework, inspired by realist synthesis and introduced in Section 1, that aims to untangle the contexts, mechanisms, and outcomes associated with investments that link poverty reduction and rural prosperity within a broad agri-food systems perspective. Section 2 considers changes in contexts: Where are agricultural research investments most likely to be an engine of poverty reduction? Over the past 25 years, there have been profound changes in the development context of most countries, necessitating an update on strategic insights for research investment priorities relevant for the economic, political, social, environmental, and structural realities of the early 21st Century. Section 2 briefly surveys changes in these structural aspects of poverty and development processes in low-income countries, with particular attention to new drivers (e.g., urbanization, climate change) that will be of increasing salience in the coming decades. In Section 3, we turn to mechanisms: What are the plausible impact pathways and what evidence exists to test their plausibility? Poor farmers in the developing world are often the stated focus of public sector agricultural research. However, farmers are not the only potential beneficiaries of agricultural research; rural landless laborers, stakeholders along food value chains, and the urban poor can also be major beneficiaries of such research. Thus, there are multiple, interacting pathways through which agricultural research can contribute to reductions in poverty and associated livelihood vulnerabilities. This paper introduces an ex ante set of 18 plausible impact pathways from agricultural research to rural prosperity outcomes, employing bibliometric methods to assess the evidence underpinning causal links. In Section 4, we revisit the concept of desired impacts: When we seek poverty reduction, what does that mean and what measures are needed to demonstrate impact? The papers in this special issue are intended to yield insights to inform improvements in agricultural research that seeks to reduce poverty. History indicates that equity of distribution of gains matters hugely, and thus the questions of "who wins?" and "who loses?" must be addressed. Moreover, our understanding(s) of "poverty" and the intended outcomes of development investments have become much richer over the past 25 years, incorporating more nuance regarding gender, community differences, and fundamental reconsideration of the meaning of poverty and prosperity that are not captured by simple head count income or even living standard measures.