The engineering of advanced heterostructure and nanoscale semiconductor devices has made essential a detailed understanding of, and control over, the structure and properties of semiconductor materials and devices at the atomic to nanometer scale. Cross-sectional scanning tunneling microscopy provides unique and powerful capabilities for characterization of structural morphology and electronic properties in semiconductor epitaxial and device structures with spatial resolution at or near the atomic scale. The basic technique of cross-sectional scanning tunneling microscopy, and key experimental considerations, are described in this article. Some representative applications of this technique drawn from recent investigations in our laboratory of atomic-scale alloy layer and interface structure in mixed-anion semiconductor heterostructures are presented. By combining the results of scanning tunneling microscopy studies with those of other, complementary characterization techniques, it is possible to develop a detailed understanding of atomic-to nanometer-scale properties of semiconductor materials and devices and to establish correlations between atomic-scale material properties and the behavior of actual devices.