A wealth of molecular biology has been exploited in designing and interpreting experimental evolution studies with bacteriophage T7. The modest size of its genome (40 kb dsDNA) and the ease of making genetic constructs, combined with the many genetic resources for its host (Escherichia coli), have enabled comprehensive and detailed studies of experimental adaptations. In several studies, the genome was specifically altered (gene knockouts, gene replacements, reordering of genetic elements) such that a priori knowledge of genetics and biochemistry of the phage could be used to predict the pathways of compensatory evolution when the modified phage is adapted to recover fitness. In other work, the phage has been adapted to specific environmental conditions chosen to select phenotypic outcomes with a quantitative basis, and the molecular bases of that evolution have been explored. Predicting the outcomes of these adaptations has been challenging. In hindsight, one-third to one-half of the compensatory nucleotide changes observed during the adaptation can be rationalized based on T7 biology. This rationalization usually only applies at the genetic level-a gene product may be known to be involved in the affected pathway, but it usually remains unknown how the observed change affects activity. The progress is encouraging, but the prediction of experimental evolution pathways remains far from complete, and is still sometimes confounded by observation when an adaptation yields a completely unexpected outcome.