Cilomilast (Ariflo) is an oral selective phosphodiesterase (PDE) IV inhibitor under development by GlaxoSmithKline Pharmaceuticals for treatment of COPD. After the demise of Merck's PDE-IV inhibitor (licensed from Celltech Group) in April 2003, Ariflo has emerged as the frontrunner in this new class of agents for inflammatory airways diseases, such as COPD. GlaxoSmithKline filed for drug approval with the US FDA at the end of 2002 and in January 2003 with the European Medicines Evaluation Agency (EMEA). In October 2003 the FDA issued an approvable letter for use of Ariflo in maintenance of lung function in COPD patients poorly responsive to salbutamol, despite an earlier decision by the FDA advisory panel to reject approval. Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilastsuppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo.