The advent of MRI has made a remarkable progress in the understanding of age-related brain changes providing a noninvasive tool to study in vivo the normally aging individuals at multiple time points. However, conventional MRI techniques are unable to detect and quantify age-related microstructural changes that have been documented at the post-mortem examination of brain tissues. More sophisticated, quantitative MR techniques such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy have been shown to be sensitive to microstructural and metabolic changes that occur in gray and white matter over the course of life span. This review highlights some of these innovative, quantitative MR techniques that are particularly relevant for the study of occult age-related brain tissue changes. Characterization of the in vivo patterns of molecular and cellular changes that occur in the normal aging brain is of crucial importance to understand the pathophysiology of normal cognitive decline and to interpret observed changes in neurodegenerative diseases.