Chloroquine and hydroxychloroquine are quinoline drugs used for treatment and prevention of malaria. They are also diseasemodifying antirheumatic drugs used for the treatment of various autoimmune diseases: rheumatoid arthritis, systemic lupus erythematosus, porphyria cutanea tarda, primary Sjogren syndrome, Lyme arthritis and antiphospholipid syndrome. Over the past two decades, numerous studies have identified antitumor activities of antimalarial drugs. The vast majority of studies focused on the sesquiterpene lactones (artemisinines) and 4-aminoquinolines. Their anticancer effects were evaluated as a part of ReDO project (Repurposing Drugs in Oncology). There are also a large number of reports on natural products with antimalarial and concomitant anticancer activity, produced by more than hundred species. Numerous preclinical and clinical studies have been conducting to elucidate the efficacy and safety profile of chloroquine or hydroxychloroquine in the therapy of different cancer types, alone or in combination with conventional antitumor drugs, radiotherapy or other therapeutic protocols. Many studies confirmed that they enhanced effects of anticancer drugs in a synergistic manner via inducing apoptosis and/ or switching off autophagic and angiogenic machineries. However, they are considered more as potential chemotherapy and radiotherapy sensitizers rather than antineoplastic drugs. Maybe they will become soon old drugs with new uses.