: Phosphodiesterase 10 (PDE10) is one of at least 11 different PDE families, which are the enzymes that degrade adenosine 3',5'-cyclic monophosphate (cAMP) and/or guanosine 3',5'-cyclic monophosphate (cGMP) by hydrolyzing the phosphodiester bonds. Inhibition of PDE10A represents a molecular target in the treatment of conditions that would benefit from the increase of the level of cAMP and/or cGMP such as neurological and psychiatric disorders, cancer, and diabetes.: The present article reviews the patent literature on PDE10A inhibitors (PDE10AIs) from 2014 to present and PDE10AI chemotypes from different chemical classes: heteroaryl- and aryl-nitrogen-heterocyclic compounds, unsaturated nitrogen-heterocyclic compounds with specific substituents such as pyrazolopyrimidine, aryloxymethyl cyclopropane, pyridizinone, imidazopyridine, triazoles and imidazo[2,1-a]isoidole. The article presents the potency of PDE10AIs, their efficacy in animal models, and their clinical utility in the treatment of schizophrenia. Therapeutic patents for the treatment of cancers, precancerous conditions, and diabetes were also collected.: Several potent PDE10AIs have been described so far; however, clinical trials have shown that without preclinical optimization, the benefit of PDE10AIs in the treatment of schizophrenia is confounded by a high placebo effect. Understanding of the requirements for PDE10AIs constitutes a challenging but promising field of drug discovery and development.