The Wnt/β-catenin pathway is highly regulated to ensure the correct activation of target genes. In the absence of Wnt stimulation, the transcriptional coactivator β-catenin is degraded by a multiprotein "destruction complex" that includes tumor suppressors Axin and adenomatous polyposis coli (APC), Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase β-TrCP. The complex generates a β-TrCP recognition site by phosphorylating a conserved Ser/Thr-rich sequence near the β-catenin amino terminus, a process that requires scaffolding of the kinases and β-catenin by Axin. Ubiquitinated β-catenin is degraded by the proteasome. The molecular mechanisms underlying several aspects of destruction complex function, particularly the role of APC, are poorly understood. This review discusses the molecular mechanisms of destruction complex function and potential roles of APC in β-catenin destruction.The Wnt/β-catenin pathway is highly regulated to ensure the correct activation of target genes. In the absence of Wnt stimulation, the transcriptional coactivator β-catenin is degraded by a multiprotein "destruction complex" that includes tumor suppressors Axin and adenomatous polyposis coli (APC), Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase β-TrCP. The complex generates a β-TrCP recognition site by phosphorylating a conserved Ser/Thr-rich sequence near the β-catenin amino terminus, a process that requires scaffolding of the kinases and β-catenin by Axin. Ubiquitinated β-catenin is degraded by the proteasome. The molecular mechanisms underlying several aspects of destruction complex function, particularly the role of APC, are poorly understood. This review discusses the molecular mechanisms of destruction complex function and potential roles of APC in β-catenin destruction.