Coma and disorders of consciousness are frequently considered in terms of two linked anatomic-functional systems: the arousal system and the awareness system. The mesopontine tegmentum (namely the cuneiform/subcuneiform nuclei of the caudal midbrain and the pontis oralis nucleus of the rostral pons) and the monoamine nuclei generate signals of arousal. These signals are augmented in lateral hypothalamus and basal forebrain, which then project to the thalamus and diffusely across the cortex. The medial dorsal tegmental tract is the main conduit for the ascending arousal system to directly activate the thalamic intralaminar nuclei and modulate thalamocortical networks, while the lateral dorsal tegmental tract connects to the thalamic reticular nucleus for regulation of intrathalamic inhibitory networks. The central thalamus (particularly the intralaminar nuclei) and the mesocircuit regulate the arousal system. Lesions to any part of this system, particularly paramedian and bilateral lesions, result in a depressed level of arousal. Distinct from the arousal pathways, the awareness system runs continuously as a stream of consciousness. It consists of large-scale distributed cortical networks that are necessary for representations of the external (executive control network with the dorsal/ventral attention networks) and the internal world (executive control network in conjunction with the default network). A feature of the awareness system is that it does not capture external and internal worlds at once and instead, holds singular representations, serially moment-by-moment. The medial dorsal nucleus of the thalamus serves as the associative nuclei of the default network, and the thalamic reticular nucleus regulates the awareness system. Lesions that disrupt large-scale networks, particularly nodes of cortical hubs, result in lack of awareness. Integrative paradigms such as the integrated information theory and the global neuronal workspace models are attempts to bind awareness and arousal into a unified experience of consciousness.