The widespread use of ionic liquids (ILs) as greener solvents in analytical sciences, especially in sample pretreatment, has focused attention on exploiting their enormous potential, not only on eliminating and improving the drawbacks faced by scientists. These ionic compounds with unique physicochemical properties can be tuned through smart synthesis, combining cations and anions, so that the compound exhibits excellent properties for its intended purpose. Ionic liquids are rightly referred to as designer solvents. Validation of a newly proposed analytical methods using ionic liquids, either in sample preparation or in further analysis, is a critical process to demonstrate that a particular analytical method is fit for purpose and provides reliable and accurate results. In addition, this article specially addressed the potential toxicity of ionic liquids with the modest goal of assisting researchers in this field by expanding their target areas.