Skeletal muscle is an extremely plastic tissue that can respond to a variety of insults. If the insult is sufficient, it may reduce damage to the skeletal muscle. Damage to skeletal muscle is associated with an inflammatory response. This inflammatory response is required for optimal regeneration. There are several models used to induce damage to skeletal muscle from eccentric muscle actions to myotoxin injections. While the method of inducing damage may vary the inflammatory response is similar. Upon damage, circulating immune cells are activated and infiltrate the tissue. The first to arrive is the neutrophil followed by the macrophage. The neutrophil clears debris and releases pro-inflammatory signals which facilitate the recruitment of macrophages. Macrophages are recruited and begin as pro-inflammatory macrophages (M1) continuing to facilitate the clearance of debris before macrophage polarization occurs in which they become anti-inflammatory macrophage (M2). The anti-inflammatory macrophages facilitate the myogenic response critical for optimal regeneration. Disruptions to the inflammatory response will directly affect the ability of the skeletal muscle to recover from injury.