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The pancreatic islet secretes the hormones insulin and glucagon to regulate glucose metabolism. To generate an adequate secretory response, islet endocrine cells must receive multiple regulatory signals relaying information about changes in the internal and external environments. Islet cells also need to be made aware about the functional status of neighboring cells through paracrine interactions. All this information is used to orchestrate a hormonal response that contributes to glucose homeostasis. Several neurotransmitters have been proposed to work as paracrine signals in the islet. Most of these, however, have yet to meet the criteria to be considered bona fide paracrine signals, in particular in human islets. Here, we review recent findings describing autocrine and paracrine signaling mechanisms in human islets. These recent results are showing an increasingly complex picture of paracrine interactions in …