Moderate to severe fatty infiltration and rotator cuff atrophy are commonly associated with poor clinical outcomes and failed rotator cuff repair. Numerous animal and human studies have attempted to elucidate the etiology of fatty infiltration and rotator cuff atrophy. Mechanical detachment of the tendon in rotator cuff tears is primarily responsible. Suprascapular nerve injury may also play a role. CT, MRI, and ultrasonography are used to evaluate severity. The Goutallier staging system is most commonly used to evaluate fatty infiltration, and rotator cuff atrophy is measured using multiple techniques. The presence and severity of fatty infiltration have been associated with increasing age, tear size, degree of tendon retraction, number of tendons involved (ie, massive tears), suprascapular neuropathy, and traumatic tears. Fatty infiltration is irreversible and progressive if left untreated. Slight reversal of muscle atrophy has been noted after repair in some studies. Novel therapies are currently being evaluated that may eventually allow clinicians to alter the natural history and improve patient outcomes.