Effective treatment after cervical spinal cord injury (SCI) is imperative as so many activities of daily living (ADLs) are dependent on functional recovery of arm and hand actions. We focus on defining and comparing neurological and functional endpoints that might be used during acute or subacute Phase 2 clinical trials involving subjects with cervical sensorimotor complete SCI (ASIA Impairment Scale [AIS-A]). For the purposes of this review, the trial would examine the effects of a pharmaceutical small molecule, drug, biologic, or cell transplant on spinal tissue. Thus, neurological improvement is the intended consequence and is most directly measured by assessing neurological impairment (eg, motor aspects of the International Standards Neurological Classification of Spinal Cord Injury [ISNCSCI]). However, changes in neurological function, even if statistically significant, may not be associated with a clear functional impact (ie, a meaningful improvement in individual activity, such as independent self-care ADLs). The challenge is to measure improvement as precisely as possible (change in impairment), but to define a clinically meaningful response in the context of functional improvement (impact on activity limitations). The principal comparisons focused on elements of the ISNCSCI assessment, including upper extremity motor score and motor level. Personal activity capabilities were also examined at various time points. The data suggest that an improvement of 2 or more motor levels after cervical sensorimotor complete SCI may be a clinically meaningful endpoint threshold that could be used for acute and subacute Phase 2 trials with subjects having sensorimotor complete cervical SCI.