Abstract. Despite growing interest in the effects of landscape heterogeneity on genetic structuring, few tools are available to incorporate data on landscape composition into population genetic studies. Analyses of isolation by distance have typically either assumed spatial homogeneity for convenience or applied theoretically unjustified distance metrics to compensate for heterogeneity. Here I propose the isolation-by-resistance (IBR) model as an alternative for predicting equilibrium genetic structuring in complex landscapes. The model predicts a positive relationship between genetic differentiation and the resistance distance, a distance metric that exploits precise relationships between random walk times and effective resistances in electronic networks. As a predictor of genetic differentiation, the resistance distance is both more theoretically justified and more robust to spatial heterogeneity than Euclidean or least cost path-based distance measures. Moreover, the metric can be applied with a wide range of data inputs, including coarse-scale range maps, simple maps of habitat and nonhabitat within a species' range, or complex spatial datasets with habitats and barriers of differing qualities. The IBR model thus provides a flexible and efficient tool to account for habitat heterogeneity in studies of isolation by distance, improve understanding of how landscape characteristics affect genetic structuring, and predict genetic and evolutionary consequences of landscape change.Key words. Gene flow, graph theory, isolation by distance, isolation by resistance, landscape connectivity, landscape genetics, resistance distance. The emerging study of how landscape features affect microevolutionary processes (landscape genetics; Manel et al. 2003) will require tools that explicitly incorporate landscape heterogeneity into analyses of gene flow and genetic differentiation. Landscape characteristics may modify gene flow between pairs of subpopulations directly by affecting dispersal rates among them or indirectly by affecting the spatial arrangement of and dispersal rates among intervening subpopulations. Yet, few models are capable of integrating landscape data into predictions of population structure.For example, models of isolation by distance (Wright 1943) are among the most widely applied tools in studies of genetic differentiation in natural populations. These models have provided powerful means to explain population structure (e.g., Rousset 1997Rousset , 2000Sumner et al. 2001;Rueness et al. 2003), investigate departures from migration-drift equilibrium (Slatkin 1993;Hutchison and Templeton 1999), and address ecological questions such as whether dispersal synchronizes the dynamics of populations separated by long distances (Schwartz et al. 2002). Yet, such analyses assume homogeneous, unbounded populations, ignoring effects of range boundaries and of variation in demographic parameters within species' ranges (Maruyama 1970;Slatkin and Maruyama 1975). As Slatkin (1985) noted, most real populations are neither hom...