The shortest path approach is a well known approach in systems biology to the search of connections between nodes in molecular networks. However, little has been shown about the biological relevance of such approach. The first part of the talk will be devoted to the analysis of the shortest paths between proteins in canonical molecular pathways built in human interactome. One can enhance this approach by taking into account the betweenness centrality of nodes or paths in order to predict the unknown members of molecular pathways from the results of the genome-scale functional screens. This will be shown in the second part of the talk.