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Introduction: Multiple sclerosis (MS) is a chronic inflammatory-demyelinating and neurodegenerative disease of the central nervous system (CNS) of a putative autoimmune origin. The disease is characterized pathologically by scattered areas of peri-vascular mononuclear cell infiltrates, demyelination with various degrees of remyelination, axonal loss and gliosis that form multiple plaques throughout the brain and spinal cord, and clinically by a variety of neurological signs and symptoms disseminated in time and space. A better understanding of the immune pathogenesis of MS has led to the development of a variety of disease-modifying drugs (DMTs) capable of suppressing disease activity and reducing relapse rate and disability progression. The first injectable drugs included 3 forms of recombinant interferon-beta and glatiramer acetate. These "first line" therapies show modest but sustained effect on clinical disease activity and a favorable long-term safety profile. Several newer oral and biological drugs having various mechanisms of action have recently been introduced for MS. They demonstrate higher efficacy but harbor new, sometimes serious adverse events and risks that may limit their use and require thorough patient selection and strict safety monitoring programs. The impact of MS drugs on disease activity and appreciation of the irreversible brain damage that occurs from disease onset have led to the adoption of modern paradigms in MS therapy which include early, effective and personalized treatment, targeting towards a complete cessation of any disease activity ("no evidence of disease activity- NEDA"). This review aims to: 1. Describe current and promising future immunomodulatory drugs for MS and their place in the treatment of various forms of MS, based on the understanding of their mechanisms of action and effect on the immuno-pathological processes that lead to the damage in MS; and 2. provide guidance on individualized treatment selection based on modern paradigms of MS management.