Purpose of the Review Osteoarthritis is widely regarded as a spectrum of conditions that affect all joint tissues, typified by a common entity: cartilage loss. Here, we review recent progress and challenges in chondroprotection and discuss new strategies to prevent cartilage loss in osteoarthritis. Recent Findings Advances in clinical, molecular, and cellular characterization are enabling improved stratification of osteoarthritis subtypes. Integration of next-generation sequencing and "omics" approaches with clinically relevant readouts shows promise in delineating both subtypes of disease and meaningful trial end points. Novel delivery strategies are enabling jointspecific delivery. Summary Chondroprotection requires a whole joint approach, stratification of patient groups, and use of patient-relevant end points. Drug development should continue to explore new targets, while using modern technologies and recent knowledge to revisit unsuccessful therapeutics from the past. The overarching goal for chondroprotection is to provide the right treatment(s) for the right patient at the right time.