Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS) in which the complex interplay between inflammation and neurodegeneration determines varying degrees of neurological disability. For this reason, it is very difficult to express an accurate prognosis based on purely clinical information in the individual patient at an early disease stage. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, a comprehensive MS outcome prediction model combining multiple parameters is still lacking. Current relevant literature addressing the topic of clinical, MRI, and CSF markers as predictors of MS disability progression is reviewed here.