Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.