Much phylogenetic information has been derived from the analysis of sequence similarity in genes and proteins. These data are generally considered to be more reliable than an examination of the phylogenetic distribution of similar biologically active molecules. However, molecules can provide significant phylogenetic information when accompanied by a careful analysis of their structure, synthesis, genetics and function. Molecules may be highly structurally and functionally constrained. Thus, similar or even chemically identical molecules may be unrelated, and this may be discernible only by examination of information beyond the simple structure of the molecule. Phylogenetic variation in the synthesis of tyrosine and lysine demonstrates that chemical identity of molecules may be brought about by unrelated synthetic pathways. The widespread distribution of collagen triple helices is shown to result from convergence under structural and functional constraints. This is demonstrated by an examination of the steric constraints upon collagens and the presence of several independent families of collagen genes. Lysyl oxidase crosslinking occurs in several unrelated proteins, indicating that similarity in the post-translational modification of proteins is not evidence of homology.