We consider three issues that appear to be important in the interpretation of developmental genetics in an evolutionary context. The three issues under discussion are 1) evolutionary loss as applied to evo-devo data; 2) the limits on our ability to infer ancestry based on tree reconstruction; and 3) “type 2” errors in the assessment of homology of developmental gene expression data. Lack of consideration of any or all of these disparate issues narrows the set of hypotheses under consideration. We examine these issues through examples drawing on new data on POU domain genes as well as through reference to published work on Distal-less, engrailed and Nk2 genes.