Molecular investigations of evolutionary history are being used to study subjects as diverse as the epidemiology of acquired immune deficiency syndrome and the origin of life. These studies depend on accurate estimates of phylogeny. The performance of methods of phylogenetic analysis can be assessed by numerical simulation studies and by the experimental evolution of organisms in controlled laboratory situations. Both kinds of assessment indicate that existing methods are effective at estimating phylogenies over a wide range of evolutionary conditions, especially if information about substitution bias is used to provide differential weightings for character transformations.