Oval cells are hypothesized to be the progeny of intrahepatic stem cells, also referred to as adult liver stem cells. The mechanisms by which these cells are activated to proliferate and differentiate during liver regeneration is important for the development of new therapies to treat liver disease. Oval cell activation is the first step in progenitor-dependent liver regeneration in response to certain types of injury. This review describes what is currently known about the factors involved in oval cell activation, proliferation, migration, and differentiation.