During the COVID-19 pandemic, genomics and bioinformatics have emerged as essential public health tools. The genomic data acquired using these methods have supported the global health response, facilitated development of testing methods, and allowed timely tracking of novel SARS-CoV-2 variants. Yet the virtually unlimited potential for rapid generation and analysis of genomic data is also coupled with unique technical, scientific, and organizational challenges. Here, we discuss the application of genomic and computational methods for the efficient data driven COVID-19 response, advantages of democratization of viral sequencing around the world, and challenges associated with viral genome data collection and processing.