Pardis Sabeti and colleagues report the whole-genome sequencing of 99 Ebola virus samples from 78 patients in Sierra Leone collected during the course of the epidemic there this year (Science doi:10.1126/science.1259657; 28 August 2014). They also include comparisons to 20 Ebola virus genomes from earlier outbreaks, including three from Guinean samples. The current outbreak started in Guinea in West Africa in February 2014 and spread to Liberia, Sierra Leone and Nigeria. This work suggests direct patient-to-patient transmission from Guinea to Sierra Leone, coinciding with the first confirmed case of Ebola virus disease in Sierra Leone in late May. They further identify two distinct viral lineages in the first 12 Sierra Leone patients, who may have been infected during a funeral that they all attended. The availability of multiple samples for some patients allowed the identification of variations within a single host. By monitoring the single-nucleotide variants (SNVs) that later became fixed in other patients and increased in frequency in the population, the authors were able to systematically track the emergence of a third viral lineage. Their work suggests that the current epidemics may be explained by human-to-human transmission, following on a zoonotic transmission event from Central Africa that occurred in the past decade.