This study extends the macro-level criminological research tradition by examining the links between socioeconomic disadvantage, poverty concentration, and homicide in metropolitan and nonmetropolitan U.S. counties. Most research in this tradition has tested structural theories using urban areas as the unit of analysis. This "urban bias" has resulted in a limited understanding of the social forces driving violence in nonmetropolitan areas. To partially address this problem, we link the literature on the spatial and social organization of nonmetropolitan communities with the social isolation perspective from the urban poverty literature. We hypothesize that the spatial concentration of poverty drives up rates of homicide in both metropolitan and nonmetropolitan areas regardless of levels of socioeconomic disadvantage. Negative binomial regression for 1,746 nonmetropolitan and 778 metropolitan counties suggest that both socioeconomic disadvantage and poverty concentration elevate homicide in metropolitan areas. However, in nonmetropolitan counties only socioeconomic disadvantage has a significant impact. We conclude by discussing the implications of these differential findings for the social isolation perspective.