Potential role of circulating microRNAs (miRNAs) involved in multiple sclerosis (MS) pathogenesis, which could be useful in discriminating between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) (miR-145-5p, miR-181c-5p, miR-223-3p, miR-27a-3p, miR-326-5p, miR-92a-1-3p, let-7c, let-7d, miR-337-3p, miR-633-5p). Upregulation and downregulation of specific miRNAs influence the Th cell differentiation into pro-inflammatory Th17 and Th1 cells, which together with B cells can cross the blood–brain barrier (BBB) and migrate to the central nervous system (CNS), where they proliferate and secrete pro-inflammatory cytokines (interleukin-1 (IL-1), IL-6, IL-17, interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α)). In the CNS, different miRNAs play various roles in cytokine secretion, monocyte stimulation, or neuronal maturation. As a consequence, dysregulation of these processes causes myelin sheath damage and, eventually, neuronal loss. Red arrow—upregulation of specific miRNA in MS compared to healthy controls; increased effect exerted by a given miRNA. Blue arrow—downregulation of specific miRNA in MS compared to healthy controls; decreased effect exerted by a given miRNA.