Lyme disease (LD), the most frequently reported vector-borne disease in the United States, requires that humans, infected vector ticks, and infected hosts all occur in close spatial proximity. Understanding the spatial dynamics of LD requires an understanding of the spatial determinants of each of these organisms. We review the literature on spatial patterns and environmental correlates of human cases of LD and the vector ticks, Ixodes scapularis in the northeastern and midwestern United States and Ixodes pacificus in the western United States. The results of this review highlight a need for a more standardized and comprehensive approach to studying the spatial dynamics of the LD system. Specifically, we found that the only environmental variable consistently associated with increased LD risk and incidence was the presence of forests. However, the reasons why some forests are associated with higher risk and incidence than others are still poorly understood. We suspect that the discordance among studies is due, in part, to the rapid developments in both conceptual and technological aspects of spatial ecology hastening the obsolescence of earlier approaches. Significant progress in identifying the determinants of spatial variation in LD risk and incidence requires that: (1) existing knowledge of the biology of the individual components of each LD system is utilized in the development of spatial models; (2) spatial data are collected over longer periods of time; (3) data collection and analysis among regions are more standardized; and (4) the effect of the same environmental variables is tested at multiple spatial scales.