Background and objectives: Osteoarthritis (OA) is among the most common degenerative diseases that induce pain, stiffness and reduced functionality. Various physiotherapy techniques and methods have been used for the treatment of OA, including soft tissue techniques, therapeutic exercises, and manual techniques. The primary aim of this systemic review was to evaluate the short-and long-term efficacy of manual therapy (MT) in patients with knee OA in terms of decreasing pain and improving knee range of motion (ROM) and functionality. Materials and Methods: A computerised search on the PubMed, PEDro and CENTRAL databases was performed to identify controlled randomised clinical trials (RCTs) that focused on MT applications in patients with knee OA. The keywords used were ‘knee OA’, ‘knee arthritis’, ‘MT’, ‘mobilisation’, ‘ROM’ and ‘WOMAC’. Results: Six RCTs and randomised crossover studies met the inclusion criteria and were included in the final analysis. The available studies indicated that MT can induce a short-term reduction in pain and an increase in knee ROM and functionality in patients with knee OA. Conclusions: MT techniques can contribute positively to the treatment of patients with knee OA by reducing pain and increasing functionality. Further research is needed to strengthen these findings by comparing the efficacy of MT with those of other therapeutic techniques and methods, both in the short and long terms.