Ketamine is a versatile N-methyl-D-aspartate (NMDA)-antagonist used in various clinical settings. Ketamine dose-dependently induces psychoactive effects: at low, anti-hyperalgesic doses, these are minor or not detectable, but at subanesthetic doses, they may include dissociative, psychotomimetic, and psychedelic events. At an anesthetic dose, ketamine leads to a state of “(full) dissociation” or disconnection rather than unconsciousness, setting it apart from other anesthetics. This unique set of characteristics makes ketamine a particularly interesting substance for studying consciousness in clinical settings. Our chapter reviews ketamine’s neurophysiological effects and neuroimaging data, its potential to inform consciousness research, and its relevance in studying brain disorders involving altered states of consciousness. We trace recent advancements in understanding ketamine’s unique brain effects and report investigations that have developed neurophysiological indexes for consciousness without behavioral output (e.g., disconnected consciousness). Specifically, we discuss the most recent tool, the Explainable Consciousness Indicator (ECI), which uses machine learning to assess the presence of awareness and wakefulness. Finally, we look at future investigations that may utilize ketamine as therapeutic approach to neurological conditions, such as disorders of consciousness.