The Pacific Decadal Oscillation (PDO) is a major forcing of inter-decadal to quasi-centennial variability of the hydroclimatology of the Pacific Basin. Its effects are most pronounced in the extra-tropical regions, while it modulates the El Niño Southern Oscillation (ENSO), the largest forcing of global inter-annual climate variability. PalaeoPDO indices are now available for at least the past 500 years. Here we show that the >500 year PDO index of Shen et al. (2006) is highly correlated with inflows to the headwaters of Australia's longest river system, the Murray-Darling. We then use the PDO to reconstruct annual inflows to the Murray River back to A.D. 1474. These show penta-decadal and quasi-centennial cycles of low inflows and a possible 500 year cycle of much greater inflow variability. Superimposed on this is the likely influence of recent anthropogenic global warming. We believe this may explain the exceptionally low inflows of the past decade, the lowest of the previous 529 years.