Over the past decade, the serine/threonine kinase Akt (also known as protein kinase B) has emerged as a critical signaling molecule within eukaryotic cells. In addition to the research required for the clarification of its regulation by upstream kinases and phosphatases, progress has been made in the identification of Akt-binding partners that modulate its activation, regulate its kinase activity, and define its impact on downstream biological responses. Studies of Akt-binding molecules have highlighted novel mechanisms involved in the regulation of signaling downstream of activated phosphoinositide 3-kinase. Akt-interacting molecules may have important roles in Akt signal transduction both under physiological and pathological conditions.