Background: Aerobic capacity (VO<inf>2max</inf>) is a strong health and performance predictor and is regarded as a key physiological measure in the healthy population and in persons with multiple sclerosis (PwMS). However, no studies have tried to synthesize the existing knowledge regarding VO<inf>2max</inf> in PwMS. Objectives: The objectives of this study were to (1) systematically review the psychometric properties of the VO<inf>2max</inf> test; (2) systematically review the literature on VO<inf>2max</inf> compared with healthy populations; (3) summarize correlates of VO<inf>2max</inf>; and (4) to review and conduct a meta-analysis of longitudinal exercise studies evaluating training-induced effects on VO<inf>2max</inf> in PwMS. Data Sources and Study Selection: A systematic literature search of six databases (PubMed, EMBASE, Cochrane Library, PEDro, CINAHL and SPORTDiscus) was performed. To be included, the study had to (1) enrol participants with definite MS according to defined criteria; (2) assess aerobic capacity (VO<inf>2max</inf>) by means of a graded exercise test to voluntary exhaustion; (3) had undergone peer review; and (4) be available in English, Danish or Dutch. Study Appraisal and Synthesis Methods: The psychometric properties of the VO<inf>2max</inf> test in PwMS were reviewed with respect to reliability, validity and responsiveness. Simple Pearson correlation analysis was used to assess the relation between key study characteristics and the reported mean VO<inf>2max</inf>. The methodological quality of the intervention studies was evaluated using the original 11-item Physiotherapy Evidence Database (PEDro) scale. A random coefficient model was used to summarize individual, weighted, standardized effects of studies that assessed the effects of exercise on aerobic capacity in PwMS. Results: A total of 40 studies, covering 165 healthy controls and 1,137 PwMS, fulfilled the inclusion criteria. VO<inf>2max</inf> testing in PwMS can be considered a valid measure of aerobic capacity, at least in PwMS having low-to-mild disability, and an ∼10 % change between two tests performed on separate days can be considered the smallest reliable change (with 95 % certainty) in VO<inf>2max</inf> in PwMS. The average body-weight-adjusted VO<inf>2max</inf> was significantly lower in PwMS (25.5 ± 5.2 mL·kg−1·min−1) compared with healthy controls (30.9 ± 5.4 mL·kg−1·min−1). The analysis of VO<inf>2max</inf> correlates revealed associations with a variety of outcomes covering all levels of the International Classification of Functioning, Disability and Health (ICF) model. The meta-analysis showed that aerobic training in PwMS may improve VO<inf>2max</inf> by as much as 3.5 mL·kg−1·min−1. Conclusions: A valid and reliable test can be performed, in at least ambulant PwMS, by the gold standard whole-body maximal exercise test. Aerobic capacity in PwMS is impaired compared with healthy people, and is significantly associated with factors on all levels of the ICF model, including disease severity. Aerobic training can improve aerobic capacity in PwMS to a degree that is associated with secondary health benefits.