The routine recovery of genetic information from the Late Pleistocene has provided dramatic new views of the evolution and ecology of animal, plant and microbe populations throughout the Quaternary, and the effects of climate change, human impact and mass-extinctions. Ancient DNA has a patchy history, because the full extent of problems relating to contamination and damage has only recently been appreciated. However, recent large-scale studies of AMS carbon-dated megafaunal populations have revealed the strength of analysing genetic patterns over geological time scales. These DNA sequences provide important new data on the timing and pattern of population colonisations in the New and Old Worlds back to the Late Pliocene, as well as the extent of morphological plasticity in Quaternary populations. Finally, the recent finding that ancient DNA can be preserved in sedimentary deposits dating to the mid-Pleistocene, even in the absence of macrofossils, creates a huge range of opportunities for the integration of genetics with paleontology, ecology and archeology. Beringian sedimentary plant DNA records show a dramatic decline in diversity leading up to the Last Glacial Maximum, suggesting the New World megafaunal mass-extinction was the final point of a process initiated by climate change.