Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal diffuse fibrosing lung disease, with a mortality rate that exceeds that of many cancers. Recently, there have been many clinical trials of novel therapies for IPF. The results have mostly been disappointing, although two treatment approaches have shown some efficacy. This Review describes the difficulties of treating IPF and the approaches that have been tried or are in development, and concludes with suggestions of future therapeutic targets and strategies.