The F-box domain containing proteins is one of the super protein families in Eukaryotic cells including yeast, plant, and mammals. For example, the model plant Arabidopsis and Medicago genomes contain nearly 700 and 1000 F-box protein encoding genes, respectively, which are the two largest gene families in the plant kingdom. Excluding the N-terminal signature, the approximately 40–50 conserved amino-acid F-box motif and their C-terminal protein–protein interaction domains define the different F-box protein subfamilies. Most of the F-box proteins studied so far can interact with SKP proteins, together with Cullin and Rbx1 to form the SCF complexes, which are the classic and most well-studied E3 ubiquitin ligase complexes. Through the F-box protein C-terminal domains, the SCF complexes confer the specificity of selective protein ubiquitination and subsequent degradation by the 26S proteasome, and this process is routinely termed as the ubiquitin–protease pathway (UPP). UPP-mediated protein degradation is one of the key regulatory mechanisms for protein stability and is the major protein degradation pathway for the majority of the intracellular proteins. Since the first plant F-box gene, UFO (Unusual Floral Organs) was isolated in 1995, a collection of about 20 plant F-box genes have been identified and functionally characterised. Proteins encoded by plant F-box genes have been revealed to be functionally diverse and play a variety of roles in developmental processes including plant hormonal signal transduction, floral development, secondary metabolism, senescence, circadian rhythms, and responses to both biotic and abiotic stresses. In recent years, with the rapid improvements of new genome sequencing technologies, hundreds of F-box genes from every sequenced plant species have been identified. Comparing with the large number of F-box genes identified so far, only a handful of them have been studied in detail and the functional characterisation of the majority of F-box gene families remains unknown. This article summarises our current understanding of plant F-box proteins, including their classification and the pathways that they regulate, and seeks to lay the foundation for a systematical investigation of F-box genes in plants.