The mental status examination relies on the physician's clinical judgment for observation and interpretation. When concerns about a patient's cognitive functioning arise in a clinical encounter, further evaluation is indicated. This can include evaluation of a targeted cognitive domain or the use of a brief cognitive screening tool that evaluates multiple domains. To avoid affecting the examination results, it is best practice to ensure that the patient has a comfortable, nonjudgmental environment without any family member input or other distractions. An abnormal response in a domain may suggest a possible diagnosis, but neither the mental status examination nor any cognitive screening tool alone is diagnostic for any condition. Validated cognitive screening tools, such as the Mini-Mental State Examination or the St. Louis University Mental Status Examination, can be used; the tools vary in sensitivity and specificity for detecting mild cognitive impairment and dementia. There is emerging evidence for the validity of cognitive screening performed during telemedicine visits, but it should not replace in-person evaluation of patients who have comorbidities that would preclude reliable testing via telephone or video. The workup after abnormal results of a mental status examination or cognitive screening tool is based on clinical judgment and primarily focuses on ruling out reversible causes of impairment and considering the need for further neuropsychiatric evaluation.