The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses. How the various antigen-presenting cell (APC) populations contribute to this process and how they handle danger signals determine the outcome of the generated immune responses. Importantly, liver mounted responses convey consequences not only for the local but also to systemic immunity. Here, we discuss various aspects of antigen presentation and its consequences by the non-professional APCs in the liver microenvironment.