No less than eleven sub-types of the enzyme family of phosphodiesterases (PDE; EC 3.1.4.-) are known to date, many of which exist as splice variants. They are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Roughly, the sub-types can be divided into 3 groups: one group of enzymes specifically degrades cyclic adenosine monophosphate (cAMP; PDE4, 7 and 8), another group specifically targets cyclic guanosine monophosphate (cGMP; PDE5, 6, and 9), whereas the third group of enzymes (including PDE1, 2, 3, 10, and 11) are non specific towards either cAMP or cGMP. PDEs influence a vast array of pharmacological processes, including pro-inflammatory mediator production and action, ion channel function, muscle contraction, learning, differentiation, apoptosis, lipogenesis, glycogenolysis and gluconeogenesis. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia.