BACKGROUND: The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. PATIENTS AND METHODS: We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. RESULTS: The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases > or = 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. CONCLUSION: Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infections.