The joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue. Importantly, articular cartilage pathology affects the health of the entire joint and therefore should not be considered or addressed in isolation. Treating articular cartilage lesions is challenging because left alone, the tissue is incapable of regeneration or highly functional and durable repair. Nonoperative treatments can alleviate symptoms associated with cartilage pathology but are not curative or lasting. Current surgical treatments range from stimulation of intrinsic repair to whole-surface and whole-joint restoration. Unfortunately, there is a relative paucity of prospective, randomized controlled, or well-designed cohort-based clinical trials with respect to cartilage repair and restoration surgeries, such that there is a gap in knowledge that must be addressed to determine optimal treatment strategies for this ubiquitous problem in orthopedic health care. This review article discusses the basic science rationale and principles that influence pathology, symptoms, treatment algorithms, and outcomes associated with articular cartilage defects in the knee., Competing Interests: J.P.S. reports grants and personal fees from Arthrex, Inc., grants from DePuy Synthes, other from Journal of Knee Surgery, grants from National Institutes of Health (NIAMS and NICHD), personal fees and other from Thieme, grants from U.S. Department of Defense, other from AO Foundation, other from American Orthopedic Association, other from AO North America, grants from Coulter Foundation, other from Mid-America Orthopedic Association, personal fees from Orthopedic Designs North America, personal fees from Smith and Nephew outside the submitted work. A.M.S. reports personal fees from Arthrex, Inc., personal fees from Musculoskeletal Transplant Foundation outside the submitted work. J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from AthleteIQ, grants from ConforMIS, personal fees from CONMED Linvatec, grants from Coulter Foundation, grants from DePuy Synthes, grants and personal fees from Eli Lilly, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Foundation, grants from National Institutes of Health (NIAMS & NICHD), grants from Purina, grants from Sites Medical, personal fees and other from Thieme, grants from TissueGen Inc, personal fees from Trupanion, grants from U.S. Department of Defense, grants from Zimmer-Biomet, outside the submitted work; In addition, Dr. Cook has a patent US Patent #10,039,277 with royalties paid from Musculoskeletal Transplant Foundation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)