The application of room-temperature ionic liquids (RTILs) as (co)solvents and/or reagents is well documented. However, RTILS also have “nonsolvent” applications in biotransformations and organocatalysis. Examples are the anchoring of substrates to RTILs; ionic-liquid-coated enzymes (ILCE) and enzyme–IL colyophilization; the construction of biocatalytic ternary reaction systems; the combination of enzymes, RTILs, membranes, and (bio)electrochemistry; and ionic-liquid-supported organocatalysts. These strategies provide more robust, more efficient, and more enantioselective bio- and organocatalysts with many practical applications. As shown herein, RTILs offer a wide range of promising alternatives to conventional chemistry.