Neutrophils guarantee a prompt and robust host response to pathogens. Yet, overshooting neutrophil activation leads to tremendous collateral damage in tissues. In advanced chronic liver disease (ACLD), neutrophils are exposed to the highly immunogenic milieu of the portal circulation prior to entering the liver sinusoids. In alcohol-related liver disease (ALD), neutrophils occupy a central role and therefore mechanisms regulating neutrophil activity pose a possible therapeutic target.