Over the coming decades nondestructive biochemical imaging by magnetic resonance imaging (MRI) will provide an adjunct or surrogate for the destructive histologic and biochemical assays used today. A number of MRI methods demonstrate image contrast that, although influenced by the biochemical composition, is not normally specific to a particular measure of the biochemical state. The most widely used of these is T2-weighted imaging, which variably reveals collagen ultrastructure, hydration (or collagen content), and, to a lesser extent, glycosaminoglycan (GAG) concentration (each of these biochemical metrics is an important determinant of the functional integrity of cartilage). The lack of specificity of this technique (and others discussed herein) confounds efforts to improve strategies for evaluating cartilage. However, three methods permit a very specific measure of the cartilage biochemical state. Each of these three methods, explored in detail in this article, is rooted in a biophysical theory that relates the image signal intensity to a specific biochemical feature. Proton-density imaging directly measures water content (hydration), a parameter that might increase approximately 5% with significant degeneration. Magic-angle imaging, in which the angle dependence of T2 is measured, can provide a specific measure of collagen (or macromolecular) ultrastructure. The difficulty in getting the angle dependence presently precludes its use clinically. Delayed gadolinium-enhanced MRI of cartilage provides a specific measure of the distribution of GAGs. This method measures the distribution of a charged contrast agent, which in turn reflects the distribution of charge associated with GAG. This technique can be used in a clinical setting, and ongoing studies will explore its utility in monitoring therapeutic efficacy and disease progression. Although none of these techniques are presently in routine clinical use, emerging data provide promise that the future will see patient-specific biochemical analysis of cartilage, an outcome almost unimaginable 20 years ago.