Articular cartilage is a complex connective tissue with the fundamental functions of load bearing, shock absorption and lubrication in joints. However, traumatic events, aging and degenerative pathologies may affect its structural integrity and function, causing pain and long-term disability. Osteoarthritis represents a health issue, which concerns an increasing number of people worldwide. Moreover, it has been observed that this pathology also affects the mechanical behavior of the articular cartilage. To better understand this correlation, the here proposed review analyzes the physiological aspects that influence cartilage microstructure and biomechanics, with a special focus on the pathological changes caused by osteoarthritis. Particularly, the experimental data on human articular cartilage are presented with reference to different techniques adopted for mechanical testing and the related theoretical mechanical models usually applied to articular cartilage are briefly discussed.