Understanding why some cellular components are conserved across species, while others evolve rapidly is a key question of modern biology. Here we demonstrate that in S. cerevisiae proteins organized in cohesive patterns of interactions are conserved to a significantly higher degree than those that do not participate in such motifs. We find that the conservation of proteins within distinct topological motifs correlates with the motif's inter-connectedness and function and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate.