Etiologic and pathogenetic factors for rotator cuff tendinopathy, although often compartmentalized to intrinsic or extrinsic causes, have multifactorial roots. The development of animal models for the study of rotator cuff disease has increased the fund of knowledge regarding this disease and has paved the way for future studies. Further multidisciplinary studies at molecular, biomechanical, and clinical levels should be undertaken to enhance the understanding of this common disorder. Ultimately, the goals of improved care, increased comprehension, and prevention of rotator cuff tendinopathy are attainable.