The predicted protein encoded by the APJ gene discovered in 1993 was originally classified as a class A G protein coupled orphan receptor but was subseqently paired with a novel peptide ligand, apelin-36 in 1998. Substantial research identified a family of shorter peptides activating the apelin receptor including apelin -17, apelin-13 and [Pyr1]apelin-13, with the latter peptide predominating in human plasma and cardiovascular system. A range of pharmacological tools have been developed including radiolabelled ligands, analogues with improved plasma stability, peptides and small molecules including biased agonists and antagonists, leading to the recommendation that the APJ gene be renamed APLNR and encodes the apelin receptor protein. Recently, a second endogenous ligand has been identified and called Elabela/Toddler, a 54 amino acid peptide originally identified in the genomes of fish and humans but misclassified as non-coding. This precursor is also able to be cleaved to shorter sequences (32, 21 and 11 amino acids), and all are able to activate the apelin receptor and are blocked by apelin receptor antagonists. This review summarises the pharmacology of these ligands and the apelin receptor, highlights the emerging physiological and pathophysiological roles in a number of diseases and recommends that Elabela/Toddler is a second endogenous peptide ligand of the apelin receptor protein.