We evaluated use of MODIS 250 m imagery for remote lake monitoring in Maine. Despite limited spectral resolution (visible red and near infrared bands), the twice daily image capture has a potential advantage over conventionally used, often cloudy Landsat imagery (16 day interval) when short time windows are of interest. We analyzed 364 eligible (≥100 ha) Maine lakes during late summer (Aug–early Sep) 2000–2011. The red band was strongly correlated with natural log-transformed Secchi depth (SD), and the addition of ancillary lake and watershed variables explained some variability in ln(SD) (R² = 0.68–0.85; 9 models). Weak spectral resolution and variable lake conditions limited accurate lake monitoring to relatively productive periods in late summer, as indicated by inconsistent, sometimes weak regressions during June and July when lakes were clearer and less stable (R² = 0.19–0.74; 8 models). Additionally, SD estimates derived from 2 sets of concurrent MODIS and Landsat imagery generally did not agree unless Landsat imagery (30 m) was resampled to 250 m, likely owing to various factors related to scale. Average MODIS estimates exceeded those of Landsat by 0.35 and 0.49 m on the 2 dates. Overall, MODIS 250 m imagery are potentially useful for remote lake monitoring during productive periods when Landsat data are unavailable; however, analyses must occur when algal communities are stable and well-developed, are biased toward large lakes, may overestimate SD, and accuracy may be unreliable without non-spectral lake predictors.