OBJECTIVE Attempts to evaluate knee cartilage damage and progression seem logical in osteoarthritis research. Magnetic resonance imaging allows for precise visualization of joint structures such as cartilage, bone, synovial tissues, ligaments and menisci, and their pathologic changes. RESULTS Recent advances in magnetic resonance technology have enabled researchers to evaluate cartilage damage and progression over the cross-sectional and longitudinal planes. Although anatomic changes can be seen, for many years the quantification of the cartilage changes has been the real challenge. Quantitative assessment of cartilage morphology using magnetic resonance imaging with fat-suppressed gradient echo sequences and digital postprocessing techniques provides high accuracy and adequate precision for cross-sectional and longitudinal studies in osteoarthritis patients. Recent data on precision, reliability, and sensitivity to change of quantitative parameters of cartilage morphology in osteoarthritis are presented in this review. Longitudinal studies currently available suggest that changes of cartilage volume, potentially as much as 5% per year, occur in osteoarthritis in most knee compartments, exceeding the variability of these measurements. CONCLUSIONS Magnetic resonance imaging provides reliable and quantitative data on cartilage status throughout all compartments of the knee, and robust acquisition protocols for multicenter trials are now available. Magnetic resonance imaging technology should hopefully reduce the number of patients needed in clinical trials, improve retention of these patients, and reduce the overall costs and the length of clinical trials of treatment response to disease-modifying osteoarthritis drugs.