An important goal of phylogenetics is to be able to consistently and accurately reconstruct the historical patterns of cladogenesis among major organismic groups. Gene-scale phylogenetics is insufficient to attain this goal owing to the presence of poor resolution and incongruence in single- and few-gene phylogenies. The increasing availability of genomescale amounts of data promises to overcome the insufficiency of gene-scale phylogenetics and uncover the genealogical tapestry uniting all living organisms with unprecedented accuracy. Here, we argue that a vast increase in data size alone—although necessary—may not be sufficient to achieve the desired accuracy for three reasons: (i) the existence of short stems in the tree of life, (ii) the saturation of phylogenetic signal in molecular sequences, and (iii) the effect of systematic error on phylogenetic inference. Devising strategies to ameliorate the effect of such challenges on sequence evolution will be critical to the success of current efforts to reconstruct the tree of life.