Much progress has been made in the design and analysis of efficient algorithms for assembling the Tree of Life from present-day molecular sequences. In the first half of the talk, I will briefly review some of the mathematical techniques that have led to our current understanding of large-scale tree-building algorithms. Prior rigorous results have typically relied on models of molecula r evolution that are too simplistic. In the second half, I will discuss recent w ork on the theoretical analysis of more realistic settings, including (time perm itting) mutation rate variation across sites, insertion-deletion events and inco mplete lineage sorting.