Physiological studies of ecology and evolution offer great promise for mechanistic understanding and hypothesis testing in the post-genomic era.  Molecular methods allow detailed descriptions of gene expression in response to environmental change, historical patterns of genetic variation at neutral molecular markers, and statistical tests for adaptive evolution.  In addition, experimental manipulations using transformation or genetic approaches enable tests of ecological functions of individual genes, as well as fitness comparison of allelic differences in natural populations.  Experimental studies of the genes that matter in ecology are facilitated by positional cloning, genetically undisturbed populations, and the opportunity to manipulate known genotypes growing in their natural environment.  We illustrate these approaches in Boechera, a perennial wild relative of Arabidopsis native to undisturbed habitats in western North America.  Using these approaches, ecological genetic studies of drought tolerance, insect resistance, and flowering phenology show consistent evidence for local adaptation among populations.