Cancer development is a multifactorial process resulting from the aberrant activation of multiple signaling pathways. It has become increasingly clear that the coordination of the signaling events leading to cancer formation and progression is under the control of macromolecular transduction complexes organized by scaffolding proteins. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins involved in the spatio-temporal activation of pathways controlling cancer cell proliferation, cell survival, and invasion. Mutations or altered expression of AKAP coding genes results in unregulated signaling associated with oncogenesis, cancer maintenance, and metastasis. This review will focus on recent advances illustrating the role of AKAPs in cancer pathophysiology as well as on their potential as therapeutic targets.