Protein-protein interactions play a crucial role in numerous Vital cell functions. However protein-protein interactions are also responsible for pathological formation of protein aggregates, which determine the development of several diseases. The key role of protein-protein interactions for manifestation of numerous cell functions attracts much attention to protein complexes as perspective drug targets. So design or discovery of small molecules that would regulate protein-protein interactions represents great pharmacological interest. The recent progress in understanding of mechanism protein-protein interaction, including role of flexibility of protein-protein interfaces, thermodynamic of complex formation, discovery of small molecules modifying protein-protein interactions, the advantages and limitation of protein-protein inhibitors as potential drugs are discussed in this review.