The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate the multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP and TAZ, consequently disabling their transcriptional coactivation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins. Like many signalling proteins, Hippo pathway proteins are modular and utilise various interaction and catalytic domains to transmit signals and regulate transcription of target genes, often in a context-dependent fashion. In this review we outline the major protein components and focus on the structure and function of some of the key Hippo pathway domains in vertebrates.