This paper summarizes the characteristics of regional-scale nitrogen (N) flow models. The regional scale is generally considered to be an area that ranges from more than 10 km2 to the size of a continent. Parameterization is the key process in creating a regional-scale model. During parameterization, transfer functions that reflect the controlling factors must be created at the target scale because the influence of different factors will change with the size of the scale. Watersheds are the most useful unit for evaluating overall N discharge; however, regional activity data is most often available for municipal units. Thus, municipal units must be reaggregated into watershed units. A longer time period is desirable to normalize seasonal and annual variations at regional scales. Parameters that influence N flow must match the investigated spatial and temporal scales. Given the need to use a range of parameters that vary in terms of the quality of the data, models exhibit inevitable uncertainties. Quantification of the uncertainties and verification of the estimated results are required. Error propagation, the Monte Carlo simulation method and maximum and minimum values have been used to obtain different threshold values of uncertainty. To verify regional-scale N flow models, the following five approaches have been used or proposed: (1) calibration of the model by detailed monitoring at multiple sites, (2) verification of the most important process of the extrapolation mechanisms, (3) verification of the N budget, paying particular attention to water quality, (4) comparison with the results quantified by different models, (5) comparison with aerial or satellite image analysis. As regional-scale modeling of N flow will become more important in the future, it is important to develop models than can accurately estimate N dynamics at this scale.