This paper provides an incisive review of paleoclimate science and its relevance to natural-resource management within the Murray-Darling Basin (MDB). The drought of 1997-2010 focussed scientific, public and media attention on intrinsic climate variability and the confounding effect of human activity, especially in terms of water-resource management. Many policy and research reviews make statements about future planning with little consideration of climate change and without useful actionable knowledge. In order to understand future climate changes, modellers need, and demand, better paleoclimate data to constrain their model projections. Here, we present an insight into a number of existing long-term paleoclimate studies relevant to the MDB. Past records of climate, in response to orbital forcing (glacial-interglacial cycles) are found within, and immediately outside, the MDB. High-resolution temperature records, spanning the last 105 years, exist from floodplains and cave speleothems, as well as evidence from lakes and their associated lunettes. More recently, historical climate records show major changes in relation to El Niño-Southern Oscillation cycles and decadal shifts in rainfall regimes. A considerable body of research currently exists on the past climates of southeastern Australia but, this has not been collated and validated over large spatial scales. It is clear that a number of knowledge gaps still exist, and there is a pressing need for the establishment of new paleoclimatic research within the MDB catchment and within adjacent, sensitive catchments if past climate science is to fulfil its potential to provide policy-relevant information to natural-resource management into the future.