Multiple sclerosis (MS) presents profound challenges beyond motor impairments, with cognitive deficits specifically attention dysfunction and chronic fatigue severely impacting patient quality of life. Recent psychophysical findings reveal that attentional impairments are phenotype-specific: patients with relapsing-remitting MS (RRMS) primarily exhibit exogenous (environmental) attentional deficits, whereas those with secondary progressive MS (SPMS) suffer from endogenous (voluntary) attentional impairments. This distinction suggests divergent underlying neurobiological mechanisms linked to active inflammation in RRMS and neurodegeneration in SPMS. Crucially, cognitive fatigue acts as a potent predictor of attentional performance, particularly in long-standing disease, rather than being a mere secondary symptom. These findings underscore the necessity of integrating regular cognitive screening and multi-target therapeutic protocols into standard MS management. Addressing the complex interplay between fatigue and attention is essential to mitigate functional decline and improve psychosocial outcomes in this vulnerable population