Unilateral spastic cerebral palsy, caused by damage to the developing central nervous system, is characterized by motor impairments mainly lateralized to one side of the body, with hand impairments greatly contributing to functional limitations. The integrity of the motor areas and the corticospinal tract (CST) is often compromised. The specific etiology may drastically influence subsequent development of CST pathways. Here we describe the pathophysiology underlying impaired upper extremity function, with particular emphasis on the relation between CST damage and hand function. We also describe the resulting sensory and motor deficits, with an emphasis on studies of precision grip, which highlight impairments in motor execution, sensorimotor integration, motor planning, and bimanual coordination beyond dexterity impairments. We show that the type and extent of early brain damage and/or CST reorganization is highly predictive of the severity of these impairments. We discuss the clinical implications of these findings, including the intriguing possibility that the specific pathophysiology is predictive of treatment outcomes. We suggest that a ‘one-treatment fits all approach’ may be insufficient, and that future rehabilitation efforts will be best guided by closely relating treatment efficacy with the specific pathophysiology.