Tendon and ligament injuries and degenerative conditions of these soft tissues have poor healing potential and healing is often incomplete. Biocellular and orthobiologic approaches including PRP and stem cell therapies are reviewed. A review of some of the regenerative medicine science and difficulties facing physicians exploring these methods is presented. A series of cases are reviewed demonstrating the application of these principles. Clinical experience with many of these biocellular interventions is outpacing validation in basic science studies. Clinical experience dictates the need for repeated clinical and imaging evaluation and the need for repeated intervention or change in strategies when needed.