Multimeric ligands consist of multiple monomeric ligands attached to a single backbone molecule, creating a multimer that can bind to multiple receptors or targets simultaneously. Numerous examples of multimeric binding exist within nature. Due to the multiple and simultaneous binding events, multimeric ligands bind with an increased affinity compared to their corresponding monomers. Multimeric ligands may provide opportunities in the field of drug discovery by providing enhanced selectivity and affinity of binding interactions, thus providing molecular-based targeted therapies. However, gaps in our knowledge currently exist regarding the quantitative measures for important design characteristics, such as flexibility, length and orientation of the inter-ligand linkers, receptor density and ligand sequence. In this review, multimeric ligand binding in two separate phases is examined. The prerecruitment phase describes the binding of one ligand of a multimer to its corresponding receptor, an event similar to monomeric ligand binding. This results in transient increases in the local concentration of the other ligands, leading to apparent cooperativity. The postrecruitment phase only occurs once all receptors have been aligned and bound by their corresponding ligand. This phase is analogous to DNA-DNA interactions in that the stability of the complex is derived from physical orientation. Multiple factors influence the kinetics and thermodynamics of multimeric binding, and these are discussed.