The regulation of recognition events in nature via dynamic and reversible self-assembly of building blocks has inspired the emergence of supramolecular architectures with similar biological activity. Synthetic molecules of diverse geometries self-assemble in water to target biological systems for applications ranging from imaging and diagnostics, through to drug delivery and tissue engineering. Many of these applications require the ability of the supramolecular system to actively recognize specific cell surface receptors. This molecular recognition is typically achieved with ligands, such as small molecules, peptides, and proteins, which are introduced either prior to or post self-assembly. Advantages of the non-covalent organization of ligands include the responsive nature of the self-assembled structures, the ease of supramolecular synthesis and the possibility to incorporate a multiple array of different ligands through pre-mixing of the building blocks. This review aims to highlight the diversity of self-assembled nanostructures constructed from mono-disperse synthetic building blocks; with a particular focus on their design, self-assembly, functionalization with bioactive ligands and effects thereof on the self-assembly, and possible applications.