Inositol monophosphatase (IMPase) catalyses the hydrolysis of myo-inositol monophosphates to myo-inositol, which is required in the phosphatidyl inositol cell signalling pathway. Here the enzyme structure, mechanism and inhibition of IMPase are reviewed. Lithium, an effective therapy for manic depression, is an uncompetitive inhibitor. In the search for alternative inhibitors to lithium, substrate-based inhibitors, bisphosphonates, terpenoid and tropolone analogues are described.