Prolactin (PRL) and growth hormone (GH) receptors are members of the cytokine receptor superfamily that are activated by ligand-induced homodimerization. On the basis of this mechanism of activation, hormone antagonists have been developed that block the receptors in an inactive conformation. PRL and GH receptors are non-kinase receptors whose activation of signaling pathways requires participation of receptor-associated kinases, such as Janus kinases or Src kinases. Signal transduction by these receptors mainly involves the JAK/Stat pathway. In this review, we discuss the mechanism of ligand binding and receptor homodimerization as well as the involvement of molecules transducing the hormonal signal. Whenever possible, we attempt to correlate cytoplasmic features of the receptors with association and/or activation of transducer molecules or with a given biological property.