The importance of biodegradation data as part of the design of safer chemicals is presented using ionic liquids (ILs) as a model study. Structural features that promote/impede IL biodegradation, IL design strategies, methods of biodegradation analysis, properties of IL/surfactant derivatives and computational methods of predicting biodegradation are discussed. The importance of metabolite studies as part of biodegradation assays is highlighted. The relevance of applying the lessons learned developing biodegradable ILs to other chemical classes is proposed. A comprehensive appendix of IL biodegradation data published since 2010 (∼300 ILs) has been compiled.