The recent development of high throughput genomic profiling technologies such as cDNA microarrays combined with advanced computational approaches have provided basic and clinical investigators with the ability to identify and characterize high-resolution expression profiles of numerous disease states and to dissect molecular networks that underlie specific disease phenotypes. In the field of osteoarthritis (OA) and cartilage research, the application of microarray technology holds the promise that it may allow the identification of molecular signatures specific for OA in articular cartilage chondrocytes which could provide clues to the elucidation of the pathogenetic mechanisms involved or responsible for the disease. Some of these molecular signatures may also be of great value in patient management and clinical care by providing potential biomarkers of utility as diagnostic or prognostic tools and as markers of the effectiveness of disease modifying therapies for OA. The aim of this chapter is to provide an overview of the relatively few investigations that applied microarrays to the study of human articular cartilage and OA.