Estimating the rate of nucleotide and amino acid substitutions is fundamental to our understanding of the mode and tempo virus molecular evolution. It also enables us to reconstruct their natural history. The development of sophisticated statistical methods and software in molecular sequencing analysis has made it easier for biologists to test and compare various evolutionary hypotheses and infer evolutionary parameters. However, the use of these software packages as a ‘blackbox’ without paying close attention to the underlying assumptions can lead to spurious rate estimations which often result in erroneous inferences of virus evolutionary histories across different timescales. In this talk, I will show how different evolutionary processes can alter the molecular evolutionary rate of viruses over time and investigate the implications of having a time-dependent rate of evolution for reconstructing phylogenetic histories of viruses. In particular, I will discuss how rapid within-host adaptation during persistent infections, purifying selection, and site saturation can determine the changes in evolutionary rate of viruses over different timescales, from a few weeks to millions of years of evolution. I will finish by describing a newly developed tree reconstruction method which accounts for time-dependent rate effects over long timescales and describe its applications for various viral datasets. This work will build towards the goal of making more accurate estimations of the timescale of phylogenetic histories and the rate at which viruses evolve. It also further strengthens the conceptual link between phylogenetics, population genetics, and molecular evolution of viruses.