Viral infections continue to pose a significant global threat, as evidenced by numerous pandemics, including the recent COVID-19 crisis caused by SARS-CoV-2. Unlike bacteria, which have been routinely isolated and cultured for centuries, viruses remain challenging to identify, particularly in low- and middle-income regions. This challenge is pronounced in Africa, which bears a disproportionately high burden of viral diseases due to various confounding factors and limited diagnostic resources. This chapter reviews advances in high-throughput approaches, particularly next-generation sequencing (NGS) and whole-genome sequencing (WGS), and their application in viral research across Africa. We discuss recent African studies utilizing these technologies to investigate viral infections and evolution, highlighting their advantages, findings, challenges, limitations, and recommendations. The chapter aims to inform policymakers of the critical need to invest in these innovative research tools to strengthen viral surveillance and response capabilities across the continent.