Aim The influence of anthropogenic climate change on organisms is an area of great scientific concern. Increasingly there is recognition that abrupt climate transitions have occurred over the late Quaternary; studies of these shifts may yield insights into likely biotic responses to contemporary warming. Here, we review research undertaken over the past decade investigating the response of Neotoma (woodrats) body size and distribution to climate change over the late Quaternary (the last 40,000 years). By integrating information from woodrat palaeomiddens, historical museum specimens and field studies of modern populations, we identify potential evolutionary responses to climate change occurring over a variety of temporal and spatial scales. Specifically, we characterize climatic thresholds in the past that led to local species extirpation and/or range alterations rather than in situ adaptation, and apply them to anticipate potential biotic responses to anthropogenic climate change. Location Middens were collected at about 55 sites scattered across the western United States, ranging from about 34 to 46° N and about 104 to 116° W, respectively. Data for modern populations were drawn from studies conducted in Death Valley, California, Missoula, Montana and the Sevilleta LTER site in central New Mexico. Methods We analysed faecal pellets from midden series collected at numerous cave sites across the western United States. From these we estimated body mass using techniques validated in earlier studies. We compared body size fluctuations at different elevations in different regions and integrated these results with studies investigating temperature–body size tradeoffs in modern animals. We also quantify the rapidity of the size changes over the late Quaternary to estimate the evolutionary capacity of woodrats to deal with predicted rates of anthropogenic climate change over the next century. Results We find remarkable similarities across the geographical range to late Quaternary climate change. In the middle of the geographical range woodrats respond in accordance to Bergmann's rule: colder climatic conditions select for larger body size and warmer conditions select for smaller body size. Patterns are more complicated at range boundaries, and local environmental conditions influence the observed response. In general, woodrat body size fluctuates with approximately the same amplitude and frequency as climate; there is a significant and positive correlation between woodrat body size and generalized climate proxies (such as ice core records). Woodrats have achieved evolutionary rates of change equal to or greater than those needed to adapt in situ to anthropogenic climate change. Main conclusions In situ body size evolution is a likely outcome of climate change, and such shifts are part of a normal spectrum of adaptation. Woodrats appear to be subject to ongoing body size selection in response to fluctuating environmental conditions. Allometric considerations suggest that these shifts in body size lead to substantial changes in the physiology, life history and ecology of woodrats, and on their direct and indirect interactions with other organisms in the ecosystem. Our work highlights the importance of a finely resolved and long-term record in understanding biotic responses to climatic shifts.