There is a critical unmet need in the clinical implementation of valid preventative and therapeutic strategies for patients with articular cartilage pathology based on the significant gap in understanding of the relationships between diagnostic data, disease progression, patient-related variables, and symptoms. In this article, the current state of classification and categorization for articular cartilage pathology is discussed with particular focus on machine learning methods and the authors propose a bedside-bench-bedside approach with highly quantitative techniques as a solution to these hurdles. Leveraging computational learning with data toward articular cartilage pathology patient phenotyping holds promise for clinical research and will likely be an important tool to identify translational solutions into evidence-based clinical applications to benefit patients. Recommendations for successful implementation of these approaches include using standardized definitions of articular cartilage, to include characterization of depth, size, location, and number; using measurements that minimize subjectivity or validated patient-reported outcome measures; considering not just the articular cartilage pathology but the whole joint, and the patient perception and perspective. Application of this approach through a multistep process by a multidisciplinary team of clinicians and scientists holds promise for validating disease mechanism-based phenotypes toward clinically relevant understanding of articular cartilage pathology for evidence-based application to orthopaedic practice.Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.