This review focuses on the SCF (for Skp1, Cdc53/Cullin, F box receptor) ubiquitin ligase complex, which plays a key role in marking regulatory proteins for destruction by the 26S proteasome. The review covers the identification and characterization of SCF components, their architecture, regulation, substrates, mechanism of action, and functional diversification. SCF complexes are composed of four subunits: Skp1, Cdc53/Cullin, Roc1/Rbx1/Hrt1, and F box proteins. These subunits interact to form a heterotetrameric ubiquitin ligase, with Skp1 linking Cdc53/Cullin to F box proteins. The review discusses the role of post-translational modifications in regulating SCF activity and the requirement for substrate phosphorylation before binding to SCF. It also explores the mechanism of ubiquitin transfer from Cdc34 to the substrate and the assembly of multiubiquitin chains. The review highlights the diversity of SCF function, with different F box proteins forming distinct SCF complexes that target specific substrates for degradation.This review focuses on the SCF (for Skp1, Cdc53/Cullin, F box receptor) ubiquitin ligase complex, which plays a key role in marking regulatory proteins for destruction by the 26S proteasome. The review covers the identification and characterization of SCF components, their architecture, regulation, substrates, mechanism of action, and functional diversification. SCF complexes are composed of four subunits: Skp1, Cdc53/Cullin, Roc1/Rbx1/Hrt1, and F box proteins. These subunits interact to form a heterotetrameric ubiquitin ligase, with Skp1 linking Cdc53/Cullin to F box proteins. The review discusses the role of post-translational modifications in regulating SCF activity and the requirement for substrate phosphorylation before binding to SCF. It also explores the mechanism of ubiquitin transfer from Cdc34 to the substrate and the assembly of multiubiquitin chains. The review highlights the diversity of SCF function, with different F box proteins forming distinct SCF complexes that target specific substrates for degradation.