Display omitted •Focus on disease-modifying approaches for intra-articular drug delivery.•Polymeric particles as platforms for sustained and controlled drug release.•In vivo delivery of nucleic acids for cartilage preservation and regeneration.•Stem cell-based tissue-engineered products for cartilage regeneration. Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, current IA-injected drugs are rapidly cleared and do not significantly affect the course of joint disease. In this review, we highlight recent developments in IA therapy, with a special emphasis on current and emerging therapeutic carriers and their potential to deliver disease-modifying treatment modalities for arthritis. Recent IA approaches concentrate on platforms that are safe with efficient tissue penetration, and readily translatable for controlled and sustained delivery of therapeutic agents. Gene therapy delivered by viral or non-viral vectors and cell-based therapy for cartilage preservation and regeneration are being intensively explored.