This review surveys recent achievements of molecular computer modeling in understanding spatial structure, dynamics, and mechanisms of functioning of transmembrane α-helical dimers in membranes. The factors driving self-association of hydrophobic helices in the membrane milieu are considered with examples of their applications to biologically relevant problems. The emphasis is made on the recent results, which help to understand important aspects of structurefunction relations for these systems and their biological activity. Limitations and shortcomings of the methods, along with their perspectives in design of new membrane active agents, are discussed. © 2011 Elsevier Inc. All Rights Reserved.