This comprehensive review discusses salinomycin, a polyether antibiotic identified as a potent agent against cancer stem cells (CSCs) and multidrug-resistant tumors. Salinomycin functions by disrupting key oncogenic signaling pathways including Wnt/β-catenin, Notch, Hedgehog, and Akt, reducing CSC viability and enhancing sensitivity to standard chemotherapeutics. Mechanistically, it induces apoptosis, autophagy, and