Knee osteoarthritis (KOA) is a multifactorial degenerative disorder of joints, affecting the world's population over the age of 65 and with a higher prevalence in females. KOA is responsible for many age associated joint problems such as stiffness and pain. Conventional methods for managing KOA such as nonsteroidal anti-inflammatory drugs (NSAID) may not improve pain or alter the disease progression and may have adverse side effects. Non-pharmacological management of OA is fundamental to management of functional limitations and provides effective symptom relief but has not shown that disease progression can be altered. Regenerative medicine is a relatively new approach which aims to induce cellular regeneration and promote self-healing through minimally invasive methods. The use of regenerative medicine slowed the progression of KOA and revealed significant improvements, yet further investigations are required to optimize the outcomes. Nutritional and metabolic aspects such as supplementations, vitamins and minerals were proven to have an impact on the progression of KOA. Genetic variations are rapidly inspected to identify any potential influence of these variations in the predisposition and diagnosis of KOA. Further supporting evidence suggests the potential influence of metabolic, nutritional and genetic aspects in optimizing the outcomes of regenerative medicine in the management of KOA.