Biological systematics has undergone dramatic changes in the last 60 years. Darwin had already used the tree of life metaphor to describe evolution in On the Origin of Species, but it was not until the first rigorous tree reconstruction techniques were introduced in the 1950s and 1960s that biologists accepted the idea of basing classification strictly on “phylogenetic relationship,” the branching of evolutionary lineages. This was followed by a series of groundbreaking advances in DNA sequencing and computational methods for phylogeny reconstruction in the 1980s and 1990s, spurring a flood of empirical studies of the tree of life. At the same time, the power of phylogenies in addressing questions in comparative biology was discovered in a wide range of disciplines, making phylogenetic inference an essential tool across the life sciences. A lot of empirical work still remains in most organism groups before the major branches in the tree of life are accurately characterized, but in the more well-studied groups, biologists are now shifting their focus from phylogenetic relationships to the dating of the splits in the tree. Computational approaches are also developing rapidly, allowing the mining of huge genomic data sets in the quest for more accurate evolutionary reconstructions. In parallel with these developments, some systematists are preparing for yet another transformational change, shifting their attention from the major branches in the tree of life (the major lineages) to the charting of the finest twigs and leaves (the species). Advances in both information technology and DNA sequencing are explored in attempts to accelerate the inventory of life on the planet, with the hope of completing our chart of the tree of life in time to save biological diversity for the future. Increasingly, people are becoming aware that this is not merely a question of ethics but that, ultimately, the survival of mankind may be on the line.