The identification of biomarkers has become increasingly important in our fundamental understanding of the molecular basis for disease and subsequently in the advancement of modern medicine. Biomarkers have been identified in a plethora of normal and pathologic conditions and are most often found in blood, tissue, or synovial fluid. Orthopaedic research has more recently focused on biomarkers of cartilage and joint diseases, with an emphasis on understanding the molecular underpinnings of their pathophysiology. This article focuses on the biomarkers identified to date in several select knee pathologies and how further research can contribute to new diagnostic tools and targeted therapeutics.