The liver is found inferior to the diaphragm and occupies most of the abdomen's right upper quadrant (RUQ). It is mostly intraperitoneal, from the fifth intercostal space in the midclavicular line to the right costal margin. The superior posterior aspect of the liver contains a bare area where the diaphragm and inferior vena cava are found (see Image. The Liver). The rest of the liver is covered by the visceral peritoneum, which meets the diaphragm at the border of the bare area, forming the coronary ligament. The inferior liver is closely associated with the gallbladder and right kidney (see Image. Inferior Surface of the Liver). Another ligament of mention is the Falciform ligament, which splits the liver into anatomic left and right along the anterior aspect. The falciform ligament's free-form edge contains the liver's round ligament, which is the remnant of the embryonic umbilical vein. Anatomically, the liver has 4 lobes: right, left, caudate, and quadrate. The caudate lobe is demarcated medially by the ligamentum venosum, posteriorly by the inferior vena cava, and anteriorly by the porta hepatis (see Image. Posterior and Inferior Surfaces of the Liver). The ligamentum venosum is the remnant of the embryonic ductus venosus. The quadrate lobe is anterior to the porta hepatis and lateral to the round ligament of the liver and is closely associated with the gallbladder. However, these anatomic lobes do not correlate to the boundaries of the 8 functional sub-divisions of the liver, which are divided according to the blood supply.

The functional unit of the liver is the lobule. Liver lobules are collections of hepatocytes in a hexagonal shape, with the center being a central vein. Within the lobules, the hepatocytes are arranged in cords, and in between the cords is a vascular space with a thin fenestrated endothelium and a discontinuous membrane called a sinusoid. These sinusoids contain Kupffer cells, the resident macrophage of the liver, and stellate cells, which are hepatic lipocytes. At the vertices of the hexagon is a triad of a bile duct branch, a portal vein branch, and a hepatic artery branch, referred to as a portal triad. Blood flows from the portal vein branch and hepatic artery branch across the lobule and finally into the central vein, a branch of the hepatic vein. An alternative organization of hepatocytes places the line between 2 triads at the center of a rhomboid, with the ends being central veins. This arrangement is called the portal acinus and helps describe the functional zones of the liver. Zone 1 hepatocytes immediately surround the portal tracts and are primarily involved in oxidative energy metabolism. Zone 3 hepatocytes immediately surround the central veins and are the primary location for the biotransformation of drugs. Zone 2 hepatocytes lie between zones 1 and 3 and have mixed functionality.

The liver protects the body from toxic substances absorbed from the gastrointestinal (GI) tract by processing and metabolism within the lobule. The cytochrome P-450 enzyme system catabolizes phase-I reactions, while phase-II reactions conjugate substances with substrates such as glucuronide, glutathione, and sulfate.