Quantifying the clinical impact of multiple sclerosis (MS) is a critical issue for judging experimental therapies tested in clinical trials, and, in everyday practice, for optimizing individual patient care. Proposed clinical outcome measures for MS belong to four main categories. In the first, information is based on the objective neurological examination. Examples in this category include the Expanded Disability Status Scale and related instruments, the Scripps Neurological Rating Scale and the MS Impairment Scale. The second category is represented by quantitative tests of neurological function: the most important example is represented by the Multiple Sclerosis Functional Composite. In the third category, information is provided by the patient or a family member. Measures of disability and handicap (as the Incapacity Status Scale, and the Environmental Status Scale), and generic or disease-specific quality of life instruments are included in this class. Finally, the last category consists of measures which present hybrid characteristics, such as the Ambulation Index and the Cambridge Multiple Sclerosis Basic Score. To date, no single measure has emerged as the ideal outcome measure: the main advantages and disadvantages of currently available measurement tools are discussed.