Filoviruses such as Ebola virus continue to pose a substantial health risk to humans. Advances in the sequencing and functional characterization of both pathogen and host genomes have provided a wealth of knowledge to clinicians, epidemiologists and public health responders during outbreaks of high-consequence viral disease. Here, we describe how genomics has been historically used to investigate Ebola virus disease outbreaks and how new technologies allow for rapid, large-scale data generation at the point of care. We highlight how genomics extends beyond consensus-level sequencing of the virus to include intra-host viral transcriptomics and the characterization of host responses in acute and persistently infected patients. Similar genomics techniques can also be applied to the characterization of non-human primate animal models and to known natural reservoirs of filoviruses, and metagenomic sequencing can be the key to the discovery of novel filoviruses. Finally, we outline the importance of reverse genetics systems that can swiftly characterize filoviruses as soon as their genome sequences are available.