The availability of several methods for the preparation of SCs free of other cell types has allowed recent experimentation providing new insights into the capacity of SCs to synthesize, release, and organize extracellular matrix materials, particularly those of the basal lamina. When these SC populations are combined in tissue culture with pure populations of neurons capable of directing SC function (without fibroblasts), new aspects of interrelationships between these cell types have come to light. In this brief chapter we review the results from this experimental approach during the last decade, and suggest the implications these observations have for interpreting known differences in SC functional expression in various body regions as well as for understanding certain disease processes. Of particular note is the discovery of an apparently essential linkage between the function of the SCs in organizing and relating to basal lamina and their ability to ensheathe and myelinate axons. It now appears that SC functional expression requires an alliance not only with the nerve fiber but also with the ECM through the production and organization of a basal lamina.