The liver harbors a rich, diverse spectrum of innate and adaptive immune cells. In homeostasis, these immune cells perform host defense against gut-derived pathogens and mediate tolerance to self-antigens. Following tissue injury there are complex interactions within the immune cell compartment which regulate liver regeneration and repair. Partial hepatectomy (PHx) and acetaminophen induced liver injury (AILI) are clinically relevant models of liver injury, which are commonly used to study liver regeneration. Here we discuss how the innate and adaptive immune systems influence liver regeneration and repair following acute hepatic injury.