One of the key challenges of biology in the post-genomic era is to assign function to the many genes revealed by large-scale sequencing programmes, since only a small fraction of gene function can be directly inferred from the coding sequence. Identifying interactions between proteins is a substantial part in understanding their function. The main technologies for investigating protein-protein interactions and assigning functions to proteins include direct detection intermolecular interactions through protein microarray, yeast two-hybrid system, mass spectrometry fluorescent techniques to visualize protein complexes or pull-down assays, as well as technologies detecting functional interactions between genes, such as RNAi knock down or functional screening of cDNA libraries. Over recent years, considerable advances have been made in the above techniques. In this review, we discuss some recent developments and their impact on the gene function annotation.