Ketamine, initially developed as an anesthetic, has gained attention in recent decades for its analgesic and anti-hyperalgesic properties. This chapter provides a comprehensive overview of the analgesic and anti-hyperalgesic effects of ketamine and its metabolites, examining their pharmacokinetics, pharmacodynamics, and exploring their pharmacological mechanisms and effects on brain function through functional neuroimaging studies. We found that the analgesic effects of ketamine and its metabolites are not only due to N-Methyl-D-aspartate (NMDA) receptor antagonism, but to a multiplicity of interactions in pathways and neurobiological systems. Regarding brain function, the available evidence shows that ketamine modulates cognitive, emotional, and motivational circuits that are important in acute and chronic pain processing.