The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic for which there is no established treatment available yet, has caused more than 68,000 deaths so far. Following the SARS-CoV outbreak in 2003, an Italian group described a hypothesis about the efficacy of two old drugs: Chloroquine (CQ) and Hydroxychloroquine (HCQ), against SARS-CoV and its future emergents. Later, this hypothesis was shown to be relevant in-vitro. Due to the high genetic similarity of SARS-CoV-2 and SARS-CoV, the hypothesis introduced by Savarino et al. and the further supportive in-vitro evidence served a rational ground for three different Chinese groups to test the efficacy of CQ or HCQ against SARS-CoV-2 in-vitro. These studies showed promising in-vitro efficacy of CQ and HCQ against SARS-CoV-2. Unfortunately, in the absence of sufficient clinical data on the (in)efficacy of CQ and HCQ in SARS-CoV-2 patients, the compassionate and off-label use of these medications is becoming politicized. Herein, we underline some critical features of the CQ/HCQ mechanism of action concerning SARS-CoV-2. Moreover, we put forward a hypothesis based on three lines of evidence on a probable link between zinc-deficiency/zinc correction and response to CQ/HCQ- and possibly other SARS-CoV-2 treatments.