Gene expression profiling, i.e., the systematic cataloging of messenger RNA sequences in a cell population, organ, or tissue sample, is a powerful means of generating comprehensive genome-level data sets on complex diseases. We have recently applied a systematic transcriptome-based approach in the study of healthy and diseased gingival tissues, as well in the response of peripheral blood mononuclear cells after periodontal therapy. Our data indicate that both the gingival and the circulating transcriptomes correlate with discernible phenotypic characteristics and may further our understanding of the pathobiology of periodontitis. In this chapter, we outline the laboratory steps required for the processing of gingival tissue and blood samples in view of hybridization with whole-genome microarrays.