Invasive pulmonary aspergillosis (IPA) is a serious complication of lung transplantation. Pre-mortem diagnosis is difficult and is made according to defined criteria. Most patients with a post mortem diagnosis of IPA only reach the possible or probable levels of diagnostic certainty during life. Here, we report a case of probable IPA that was refractory to conventional treatment, including amphotericin, but which responded to therapy with caspofungin. A 23-year-old man underwent heart-lung transplantation for cystic fibrosis. Ten years after transplantation he developed IPA. His condition continued to deteriorate despite treatment with itraconazole, liposomal amphotericin and flucytosine together with treatment of a concomitant infection with Pseudomonas aeruginosa. Following treatment with caspofungin there was progressive and sustained clinical and radiological improvement. No adverse reaction occurred during treatment. Caspofungin should be considered as an alternative treatment for IPA in lung transplant recipients who fail to respond to other therapy.