Coronavirus disease-2019 (COVID-19) was acknowledged as a pandemic in March 2020. COVID-19 affected substance users by aggravation of stress and reduction of substance availability. This led to the proliferation of gray market, inadvertent consumption of toxic substances, withdrawal-related suicide attempts, and even completed suicide. Among these, a silver lining was an increased treatment-seeking behavior. Tobacco is a highly debated substance in the context of COVID-19, with contradictory and controversial evidence regarding the interrelationship between the two. Nicotine affects the expression of angiotensin-converting enzyme-2 (ACE-2), which acts as a cellular receptor for the entry of SARS-CoV-2. Cholinergic nicotinic stimulation to alveolar macrophages can also reduce cytokine release. This might be helpful during the cytokine storm phase of the illness. So nicotine may be a treatment option for COVID-19. Some counterintuitive data show a reduced prevalence of smoking among COVID-19 patients in comparison to the general population. Smoking and vaping-related lung injuries are proposed to be a contributory factor for increased mortality among adult males. Vaping may further increase vulnerability by acting as a fomite source for infection due to the sharing of the device. Lockdown has increased predilection for tobacco use and also restricted substance availability and treatment access. In this situation, various behavioral managements such as distraction techniques and relaxation exercises might be helpful to handle craving. Telemedicine and app-based interventions might also be helpful in some situations.