Over the past three millennia, scholars have attempted to establish connections between localized brain damage and corresponding behavioral changes. A significant advancement in this area occurred between 1942 and 1948, when Soviet neuropsychologist Alexander Luria developed the first systematic neuropsychological assessment, comprising a battery of behavioral tasks designed to evaluate specific aspects of behavioral regulation. During and following the Second World War, Luria conducted extensive research with large cohorts of brain-injured Russian soldiers.

Among his most influential contributions was the identification of the critical role played by the frontal lobes of the cerebral cortex in neuroplasticity, behavioral initiation, planning, and organization. To assess these functions, Luria developed a range of tasks—such as the Go/no-go task, "count by 7," hands-clutching, clock-drawing task, repetitive pattern drawing, word associations, and category recall—which have since become standard elements in neuropsychological evaluations and mental status examinations.

Due to the breadth and originality of his methodological contributions, Luria is widely regarded as a foundational figure in the field of neuropsychological assessment. His neuropsychological test battery was later adapted in the United States as the Luria-Nebraska neuropsychological battery during the 1970s. Many of the tasks from this battery were subsequently incorporated into contemporary neuropsychological assessments, including the Mini–mental state examination (MMSE), which is commonly used for dementia screening.

Neuropsychological assessment has traditionally been employed to evaluate the degree of impairment in specific cognitive or functional abilities and to assist in identifying potential areas of brain damage resulting from brain injury or neurological illness. With the development of advanced neuroimaging techniques, the precise localization of space-occupying lesions can now be achieved with greater accuracy, thereby shifting the focus of neuropsychological assessment toward the evaluation of cognitive and behavioral functioning. This includes the systematic examination of the impact of brain injury or other neuropathological processes on an individual.

A central component of neuropsychological assessment involves the administration of standardized neuropsychological tests, which provide a structured means of evaluating cognitive abilities. However, neuropsychological assessment encompasses more than the mere administration and scoring of these tests and screening instruments. It is critical that such assessments also incorporate an evaluation of the individual's mental status, particularly in cases involving suspected Alzheimer's disease or other types of dementia.

Cognitive domains typically assessed include orientation, memory and new learning, general intellectual functioning, language abilities, visuoperceptual skills, and executive function. Nevertheless, comprehensive clinical neuropsychological assessment extends beyond cognitive evaluation to consider psychological factors, personality characteristics, interpersonal relationships, and the broader contextual and environmental circumstances relevant to the individual.

Assessment may be carried out for a variety of reasons, such as:

Miller outlined three broad goals of neuropsychological assessment. Firstly, diagnosis, to determine the nature of the underlying problem. Secondly, to understand the nature of any brain injury or resulting cognitive problem (see neurocognitive deficit) and its impact on the individual, as a means of devising a rehabilitation programme or offering advice as to an individual's ability to carry out certain tasks (for example, fitness to drive, or returning to work). And lastly, assessments may be undertaken to measure change in functioning over time, such as to determine the consequences of a surgical procedure or the impact of a rehabilitation programme over time.