The skin is the largest organ in the body. It provides a compliant interface for needle-free drug delivery, while avoiding major degradative pathways associated with the GI tract. These can result in improved patient compliance and sustained and controlled release compared to other standard delivery methods such as intravenous injection, subcutaneous injection, and oral delivery. Concurrently, for the treatment of skin related diseases (e.g. bacterial infection, skin cancer, psoriasis, atopic dermatitis, etc.) cutaneous application provides targeted delivery to the disease site, allowing the use of more potent therapeutics with fewer systemic side effects. Unfortunately, the outer layer of the skin -- the stratum corneum (SC) -- presents a significant barrier to most foreign material. This is particularly true for large hydrophilic molecules (>500Da), which must partition through tortuous lipid channels in the SC to penetrate deep tissue layers where the majority of skin-related diseases reside. Interestingly, over the last few decades ionic liquids (ILs) have emerged as a burgeoning class of designer solvents. ILs have been proven beneficial for use in industrial processing, catalysis, pharmaceuticals, and electrochemistry to name a few. The ability to modulate either the cation or anion individually presents an advantageous framework for tuning secondary characteristics without sacrificing the primary function of the IL. Here we report the use of novel ILs for cutaneous drug delivery. Specifically, we demonstrate their potential as potent, broad-spectrum antimicrobials, as solvents for topical delivery of hydrophilic and hydrophobic drugs, and as prodrugs to either reduce the dose-dependent toxicity of drugs that cause skin irritation or enhance delivery of macromolecules into skin and cells. Thus, our results clearly demonstrate ILs holds promise as a transformative platform for treating skin disease.