Cognitive impairment occurs in 40% to 60% of those with multiple sclerosis, with devastating effects for some. Subtle abnormalities may already be present in those with clinically isolated syndromes, but impairment tends to be more severe as the disease progresses. Difficulties with memory, information processing, and executive functions are frequent, but other cognitive skills may also be impaired. Standard markers of disease burden (T2 lesion load) do not correlate closely with these deficits, as exemplified by the finding that cognition is equally impaired in those with primary and secondary progressive disease despite very different T2 lesion loads. Searching for better predictors of cognition, Zivadinov et al (this issue, …