Background The recent COVID-19 outbreak (pandemic) has inflicted great human lives and economic losses. Aside from being abated, new surges in cases are being recorded. The sudden emergence and fulmination of the disease and its rapid spread caught the health authorities worldwide, including the developed ones, off guard, with no novel drugs available. Therefore there was no choice other than using the old drugs. Objectives This study aims to reveal the possible mechanism of action, adverse drug reactions and beneficial combination of drugs used in COVID-19 treatment Methods We undertook a comprehensive living structural review of COVID-19, searching databases, and other sources to identify literature on drugs used in the treatment of COVID-19. We analyzed the sources, publication date, type, and the topic of the retrieved articles/studies in the available search machines. Results Although a large number of literature on COVID-19 deals with pathology, clinic, and epidemiological issues, few studies that tackle pharmacology and toxicology of the drugs used could be found in the literature. At least twenty six (26) drugs, alone or in various combinations, are found in the literature to be used in various countries in the world. These drugs had been used previously for other purposes but they also possess activities that could target various steps involved in the virus invasion-replication-multiplication and leaving the cell. Pharmacokinetic fundamentals had also been applied in some combination (decrease Lopnavirs metabolism by ritonavir), but some drugs that were initially extensively used at high doses without benefiting from some of their properties are recently being abandoned (hydroxychloroquine, ionophore for Zn2+). Conclusion The literature concerning drugs used in the treatment of COVID-19 lag far behind the great number of literature that discusses diseases pathogenicity, clinical picture, and epidemiology. The World indeed had been caught unprepared for COVID-19, hence obliged to use old drugs.