Arterial spin labeling (ASL) data are typically differenced, sometimes after interpolation, as part of preprocessing before statistical analysis in fMRI. While this process can reduce the number of time points by half, it simplifies the subsequent signal and noise models (i.e., smoothed box-car predictors and white noise). In this paper, we argue that ASL data are best viewed in the same data analytic framework as BOLD fMRI data, in that all scans are modeled and colored noise is accommodated. The data are not differenced, but the control/label effect is implicitly built into the model. While the models using differenced data may seem easier to implement, we show that differencing models fit with ordinary least squares either produce biased estimates of the standard errors or suffer from a loss in efficiency. The main disadvantage to our approach is that non-white noise must be modeled in order to yield accurate standard errors, however, this is a standard problem that has been solved for BOLD data, and the very same software can be used to account for such autocorrelated noise.