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.