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The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation.