Antiviral therapies play an important role in managing both acute and chronic viral infections. Concerns about the impact of antivirals on cardiovascular health have grown over the years, particularly due to their widespread use during the COVID-19 pandemic and in long-term HIV treatment, which has highlighted potential cardiotoxic risks. This chapter explores the mechanisms underlying antiviral-induced cardiovascular toxicity, including mitochondrial dysfunction, metabolic dysregulation, endothelial dysfunction, and QT prolongation. A key example of antiviral-induced cardiotoxicity is the chronic administration of antiretroviral therapy (ART), which has been linked to dyslipidemia, insulin resistance, and an increased risk of myocardial infarction. This effect is particularly evident in ART regimens containing protease inhibitors such as ritonavir. Acute antiviral therapies, such as remdesivir that has been used for SARS-CoV-2 treatment, can lead to the development of bradycardia and arrhythmias. These examples show that careful patient monitoring, especially for individuals with pre-existing cardiovascular risk factors, is required when balancing antiviral efficacy and cardiovascular safety necessitates. Large clinical studies such as the D:A:D cohort have shown incidence, reinforcing the need for cardiovascular risk stratification in HIV treatment. Similarly, concerns about cardiovascular events related to COVID-19 antiviral treatments highlight the need to understand drug-induced endothelial activation and arrhythmias, particularly in acute infections like COVID-19. As antivirals remain integral to treatment of viral disease, a stronger understanding of the cardiovascular risks inherent in the use of antivirals will be critical for optimizing patient outcomes while minimizing cardiovascular risks.