Several polytopic α-helical membrane-integrated proteins appear to be organized in higher-ordered oligomeric complexes. While many aspects are still enigmatic, in recent years, the physiological impact of membrane protein oligomerization has been analyzed to some extent. In the present article, oligomerization of structurally well-defined membrane proteins is discussed. The available experimental information indicates the causes and physiological consequences of membrane protein oligomerization, including stabilization, cooperative functions, and control of specific activities. Based on the currently available observations, we aim to derive some general principles and discuss open questions.