Introduction. Aspects of multiple sclerosis that relate to trial design and clinical management. Biological concepts of multiple sclerosis pathogenesis and relationship to treatment. The multiple sclerosis disease process as characterized by magnetic resonance imaging -- Clinical trial methodology. Measures of neurological impairment and disability in multiple sclerosis. Health-related quality of life assessment in multiple sclerosis. Measures of gadolinium enhancement, T1 black holes and T2-hyperintense lesions on magnetic resonance imaging in multiple sclerosis. Measures of magnetization transfer in multiple sclerosis. Measurement of central nervous system atrophy in multiple sclerosis. Axonal pathology in patients with multiple sclerosis. Functional imaging in multiple sclerosis. Magnetic resonance imaging of pathway-specific structure and function in multiple sclerosis. Optical coherence tomography to monitor neuronal integrity in multiple sclerosis. Biomarkers in multiple sclerosis. The process of drug development and approval in the United States, the European Union, and Canada. Selection and interpretation of end-points in multiple sclerosis clinical trials. Clinical trial logistics. The challenge of long-term studies in multiple sclerosis: use of pooled data, historical controls, and observational studies to determine efficacy. Alternative designs for multiple sclerosis clinical trials. Ethical considerations in multiple sclerosis clinical trials. Pharmacogenetics and phamacogenomics in multiple sclerosis -- Clinical trials of multiple sclerosis therapies. Interferons in relapsing-remitting multiple sclerosis. Interferons in secondary progressive multiple sclerosis. Neutralizing antibodies directed against interferon [beta]. Glatiramer acetate as therapy for multiple sclerosis. Use of mitoxantrone to treat multiple sclerosis. Use of cyclophosphamide and other immunosuppressants to treat multiple sclerosis. Natalizumab in multiple sclerosis. High-dose methylpredisolone in the treatment of multiple sclerosis. Intravenous immunoglobulin in multiple sclerosis. Therapeutic plasma exchange for multiple sclerosis. Statins in multiple sclerosis. Stem cell transplantatation for multiple sclerosis. T cell-based therapies for multiple sclerosis and related diseases. Chemokines and central nervous system inflammation: relevance to multiple sclerosis. Sex hormones and other pregnancy-related factors with therapeutic potential in multiple sclerosis. Neuroprotection in multiple sclerosis. Combination therapy in multiple sclerosis. Fampridine in multiple sclerosis. Complementary and alternative treatments in multiple sclerosis -- Therapy in clinical practice. Disease-modifying therapy for multiple sclerosis in clinical practice. Treatment for patients with primary progressive multiple sclerosis. Use of magnetic resonance imaging in clinical management of multiple sclerosis. Fatigue in multiple sclerosis. Management of spasticity in multiple sclerosis. Management of bladder and sexual dysfunction in multiple sclerosis. Depression in multiple sclerosis. Treatment of pain, paresthesias, and paroxysmal disorders in multiple sclerosis. Rehabilitation in multiple sclerosis patients.