Osteoarthritis is the second most common disorder after heart disease. This progressive degenerative disease affects the knee joint more than any others. The exact etiology of knee osteoarthritis is not clear, however, there are many predisposing factors such as obesity, age, gender, etc., that can increase the incidence and prevalence of this disease. Early diagnosis in knee osteoarthritis is very important. Despite the variety of diagnostic methods, lack of a valid and reliable diagnostic approach to detect the disorder in early stages has always been a challenge for researchers. Establishing an efficient therapeutic protocol for these patients is another crucial challenge. Recently, in addition to conventional treatments, which are surgical and non-surgical, tissue engineering and regenerative medicine as novel therapeutic modalities have received remarkable attention. In this paper, current diagnostic and therapeutic methods for knee osteoarthritis are discussed and potential biomarkers for early diagnosis and monitoring the clinical condition are discussed.