The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks in the core of the brainstem. The reticular formation is made up of a diffuse net-like formation of reticular nuclei which is not well-defined. It may be seen as being made up of all the interspersed cells in the brainstem between the more compact and named structures.

The reticular formation is functionally divided into the ascending reticular activating system (ARAS), ascending pathways to the cerebral cortex, and the descending reticular system, descending pathways (reticulospinal tracts) to the spinal cord. Due to its extent along the brainstem it may be divided into different areas such as the midbrain reticular formation, the central mesencephalic reticular formation, the pontine reticular formation, the paramedian pontine reticular formation, the dorsolateral pontine reticular formation, and the medullary reticular formation.

Neurons of the ARAS basically act as an on/off switch to the cerebral cortex and hence play a crucial role in regulating wakefulness; behavioral arousal and consciousness are functionally related in the reticular formation using a number of neurotransmitter arousal systems. The overall functions of the reticular formation are modulatory and premotor, involving somatic motor control, cardiovascular control, pain modulation, sleep and consciousness, and habituation. The modulatory functions are primarily found in the rostral sector of the reticular formation and the premotor functions are localized in the neurons in more caudal regions.

The reticular formation is divided into three columns: raphe nuclei (median), gigantocellular reticular nuclei (medial zone), and parvocellular reticular nuclei (lateral zone). The raphe nuclei are the place of synthesis of the neurotransmitter serotonin, which plays an important role in mood regulation. The gigantocellular nuclei are involved in motor coordination. The parvocellular nuclei regulate exhalation.

The reticular formation is essential for governing some of the basic functions of higher organisms. It is phylogenetically old and found in lower vertebrates.

The human reticular formation is composed of almost 100 nuclei and contains many projections into the forebrain, brainstem, and cerebellum, among other regions. It includes the reticular nuclei, reticulothalamic projection fibers, diffuse thalamocortical projections, ascending cholinergic projections, descending non-cholinergic projections, and descending reticulospinal projections. The reticular formation also contains two major neural subsystems, the ascending reticular activating system and descending reticulospinal tracts, which mediate distinct cognitive and physiological processes. It has been functionally cleaved both sagittally and coronally.

Traditionally the reticular nuclei are divided into three columns:^{[citation needed]}

The original functional differentiation was a division of caudal and rostral. This was based upon the observation that the lesioning of the rostral reticular formation induces a hypersomnia in the cat brain, while lesioning the caudal portion causes insomnia. This study has led to the idea that the caudal portion inhibits the rostral portion of the reticular formation.^{[citation needed]}