IntroductionAlthough fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions.MethodsIn accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion.ResultsThe search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One study utilized a procedural intervention (i.e. transcranial direct current stimulation), while the other utilized a pharmacological intervention (i.e. fampridine-SR). Studies were evaluated for risk of bias, and evidence from both eligible studies was discussed.ConclusionDespite the positive results of the procedural intervention, the paucity of eligible studies and the nascent nature of the field suggests that more studies are required before firm conclusions can be drawn regarding the amenability of CF to treatment.Trial registrationThe review was registered with PROSPERO (CRD42019118706).Electronic supplementary materialThe online version of this article (10.1007/s40120-019-00158-3) contains supplementary material, which is available to authorized users.