Wnt signalling, a key pathway involved in various aspects of embryonic development, also underlies many human diseases, in particular, cancer. Research focused on signal transduction within signal-receiving cells led to the discovery of many Wnt pathway components, but study of the secretion of Wnt ligands themselves was neglected until recently. Attention was drawn to this highly regulated process by the association of aberrant Wnt levels with an increasing number of diseases. Studying the biogenesis and processing of active Wnt ligands will open new avenues for generating therapeutics to specifically target aberrant Wnt signalling. Here we review the proteins required for Wnt secretion and signalling at the plasma membrane, ending with a discussion on potential therapeutic approaches to treat Wnt-induced diseases.