Introduction This chapter describes the measurement of impairment and disability for use in MS clinical trials, rather than from a patient care perspective. Measuring impairment and disability for individual patients differs from evaluating the impact of therapies on impairment and disability. For patient care, we focus on the individual in order to alleviate suffering, prevent problems, and lessen the impact of the disease. In the latter, we assess evidence in favor of a therapy in order to determine whether that therapy is beneficial to patients in general. For patient care, clinical assessments identify problems, document the course of disease, provide etiological clues, prevent consequences of the disease, and guide therapeutic interventions. Because of the complexity of the multiple sclerosis (MS) disease process and the variety of clinical features, clinical tools are most effectively applied by skilled clinicians. Good clinical care could be viewed as a series of informal clinical trials, in which the clinician uses each patient as a study, in which the patient serves as his own control. Individualizing treatment is central to patient care, and successful response at the level of the individual patient is the goal. This ongoing “n of 1” trial is appropriate for patients, and results in many anecdotes, but is neither appropriate nor accepted for experimental studies. To evaluate the impact of treatment on impairment and disability, clinical measurements are needed that derive from a population of patients under a predefined, common protocol. Many concepts discussed in this chapter are relevant at the patient care level, but the reader should realize that optimal measures for clinical trials may differ significantly from evaluative methods for individualized patient care. Impairment and disability differ somewhat based on the specific classification system (e.g. WHO, the Nagi model, AMA, Social Security Administration (SSA)), but impairment and disability may become quite dissociated at the individual patient level. For example, a wheelchair-bound paraplegic may be working full-time, and would therefore not meet the SSA's definition of disability, while a surgeon might have a relatively minor injury to a digital nerve that limits his ability to perform critical neurosurgical techniques. Thus, definitions that seem clear, and in general can be applied to groups of impacted individuals, nevertheless fail to meet our expectations in certain cases. Thus, we often accept outcomes at the group level that suffer deficiencies at the individual level and vice versa. This compromise occurs as well with clinical trial outcomes.