The 12 kb single-stranded negative-sense rabies virus (RABV) genome exhibits unusual genomic plasticity owing to which this virus often dodges immune surveillance and is highly adaptative in new host animals. Attempts to link genome evolution, transmission and prevalence of RABV have been greatly facilitated by genomic approaches. Previously reported large-scale phylodynamic studies attempting to identify the origin of diverse RABV lineages and spill-over events have been deficient in representation from Asian countries where most human deaths due to rabies are recorded. Advancements in high-throughput DNA sequencing techniques have enabled low-cost and rapid analysis of trends in RABV genome evolution, sustenance and transmission. Here, we discuss the improvements and requirements for genome-based surveillance methods and their limitations. Ultimately, a prevention programme can be more effective if high-risk areas are identified through phylogenetic and spatiotemporal studies of human and animal rabies.