Due to the variations in morphological and architectural characteristics of fibers within a skeletal muscle, regions of a muscle may be differently affected by eccentric exercise. Although eccentric exercise may be beneficial for increasing muscle mass and can be beneficial for the treatment of tendinopathies, the non-uniform effect of eccentric exercise results in regional muscle damage and as a consequence, non-uniform changes in muscle activation. This regional muscle weakness can contribute to muscle strength imbalances and may potentially alter the load distribution on joint structures, increasing the risk of injury. In this brief review, the non-uniform effects of eccentric exercise are reviewed and their implications for training and sport are considered.