At date, research is moving for a direct SARS-CoV-2 antiviral, which will be, probably, the ideal solution to defeat the virus. In the meantime, evidences have shown that effective improvements for health status of infected patients can be found in the decrease or stop of the hyper inflammatory state. Experts have divided the SARS-CoV-2 infection in three phases. In the last one, phase 3, the most severe, the immune system goes an overdrive status and, as consequence, it launches a large-scale assault versus all the tissues. This phenomenon is known as “cytokine storm” and it can lead to a damage of organs and, in some cases to death. Several studies showed that blocking the cytokine storm or acting advance with a prevention of the phenomenon, can be effective; studies are ongoing to evaluate agents that can be able to reduce this hyperinflammatory state, as, for example, IL-6 or IL-1 inhibitors. However, other drugs that are able to block the cytokine cascade can also be considered. In this article is reported the scientific and molecular motivation related to the use of colchicine as monotherapy or in association in all three phases of infection by SARS-CoV-2 modulating the inflammatory state. Colchicine can be considered safe and effective for the treatment and prevention of Cytokine Storm in patients affected by SARS-CoV-2 infection, in particular as a remedy added to other therapeutical agents. In fact, colchicine, probably, provides a bigger benefit to all current agents and its safety profile is superior to the one provided by other drugs, such as corticosteroids and immunosuppressive drugs.