Human astrocytes differ significantly from those of rodents in size, structure, and function. Human protoplasmic astrocytes are 2.6-fold larger in diameter and extend 10-fold more GFAP-positive processes than rodent counterparts. They also propagate Ca²⁺ waves at fourfold faster speeds. Human astrocytes exhibit increased intracellular Ca²⁺ responses to purinergic and metabotropic receptor agonists. The human neocortex harbors several anatomically defined subclasses of astrocytes not present in rodents, including varicose projection astrocytes, which have long fibers with regularly spaced varicosities, and interlaminar astrocytes, which populate superficial cortical layers and extend long processes without varicosities to layers 3 and 4. Human fibrous astrocytes are larger and more complex than rodent counterparts. These structural differences suggest that human astrocytes are more complex and diverse, potentially contributing to the increased functional competence of the adult human brain. The study highlights the unique features of human astrocytes and the limitations of using rodent models to study human glial biology. The findings suggest that the unique morphology and physiology of human astrocytes may underlie many of the distinct neurological capabilities that define humans.Human astrocytes differ significantly from those of rodents in size, structure, and function. Human protoplasmic astrocytes are 2.6-fold larger in diameter and extend 10-fold more GFAP-positive processes than rodent counterparts. They also propagate Ca²⁺ waves at fourfold faster speeds. Human astrocytes exhibit increased intracellular Ca²⁺ responses to purinergic and metabotropic receptor agonists. The human neocortex harbors several anatomically defined subclasses of astrocytes not present in rodents, including varicose projection astrocytes, which have long fibers with regularly spaced varicosities, and interlaminar astrocytes, which populate superficial cortical layers and extend long processes without varicosities to layers 3 and 4. Human fibrous astrocytes are larger and more complex than rodent counterparts. These structural differences suggest that human astrocytes are more complex and diverse, potentially contributing to the increased functional competence of the adult human brain. The study highlights the unique features of human astrocytes and the limitations of using rodent models to study human glial biology. The findings suggest that the unique morphology and physiology of human astrocytes may underlie many of the distinct neurological capabilities that define humans.