The rotator cuff injury is caused by significant damage by trauma or other factors and currently recognized as a prevalent orthopedic problem. Many clinical procedures have been proposed to reduce the complication of rotator cuff injury with varying degrees of success. A literature search was conducted of PubMed and ISI Web of Knowledge using relevant keywords as well as government website for clinical trial. Platelet-rich plasma (PRP) is one of the most effective strategies for the symptomatic treatment of rotator cuff injury. Many parameters can influence the result of PRP, including intensity of rotator cuff injury, patient’s age, PRP producing strategy, and frequency and timing of PRP injections. However, some evidence supports the beneficial effect of PRP in relieving pain and restoring function, along with its minimal adverse effects, compared with using corticosteroids and other nonsurgical methods. Besides platelet-rich plasma, mesenchymal stem cells (MSCs) are another alternative that can be used to treat rotator cuff injuries. Because enough large clinical trials cannot be applied, using these biological cells have their challenges similar to PRP. In conclusion, further research is necessary to understand the potential application of both methods as safe and effective therapeutic options for rotator cuff injuries.