The G protein-coupled receptor (GPCR) superfamily plays central and diverse physiological via activation of a limited set of signal pathways. Thus, our understanding of GPCR signalling have evolved to provide insight into the molecular mechanisms mediating signal diversity, and how such complex signalling may be decoded by a cell into specific responses. The pregnant human uterus undergoes dramatic reprogramming during human labour to drive both contractions and inflammation via the action of oxytocin and prostaglandins PGE2 and PGF2alpha. Our studies on the oxytocin receptor (OTR), PGE2 receptor, EP2, and PGF2alpha receptor, FP, in term pregnancy highlight that GPCR action is exquisitely complex. This talk will discuss our evolving models of GPCR action in the term pregnant human myometrium, whereby GPCRs are pleiotropically coupled to diversify their cellular signalling. Furthermore, that during human labour, oxytocin activated OTR selectively 'rewires' distinct GPCRs to promote pro-labour responses via receptor crosstalk. This highlights a central role of diversification of GPCR activity in dynamic biological systems such the pregnant myometrium, and new avenues to harness this knowledge to generate pathway selective modulators as potential novel therapeutic strategies in management of pre-term or overdue pregnancies.