Technically, a "cortex" is an outer layer of an organ; thus, there is a cerebral cortex (in the brain) as well as an adrenal cortex (the outer layer of the adrenal gland), a renal cortex (the outer layer of the kidney), and so on. However, in common parlance, "cortex" is usually taken as a shorthand for "cerebral cortex". Likewise, the adjective "cortical" usually refers to the cerebral cortex.

The cerebral cortex forms the outer layer of the brain, including its recognizable gray, wrinkled surface. The gray substance is actually the cell bodies of nerve cells, or neurons; underneath lies the so-called white matter, formed of the output processes (axons) of these neurons. The wrinkled surface reflects the fact that, in humans and other primates, the brain has grown at a faster rate than the skull, and so the surface of the brain is folded to fit inside the skull. If the human cortex were smoothed out, it would appear as a sheet about the size of a tabloid newspaper, about 3 millimeters thick.

The cerebral cortex has left and right halves which, to a first approximation are mirror images of each other. In most cases, structures which appear on the left side (or hemisphere) have an analogous structure on the right side (or hemisphere). There are a few exceptions: notably, areas of the left hemisphere are specialized for language processing in most right-handed people. In general, sensory information from the left side of the body is processed in the right hemisphere, and vice versa; motor commands to the left side of the body also originate from the right hemisphere, and vice versa.

The cortex is often divided into large regions, called lobes, based on anatomical structure and also on function. These include the frontal lobes, the parietal lobes, the occipital lobes and the temporal lobes.