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PURPOSE OF REVIEW: Since the start of the HIV pandemic, systemic infection with Penicillium marneffei has developed from a very rare diagnosis to the third most common opportunistic infection in HIV co-infected patients in South East Asia. HIV patients who have travelled to or lived in Asia may present with this infection in nonendemic countries, and it has therefore become important for all those working in the field of HIV to recognize, understand and treat this emerging disease. RECENT FINDINGS: The clinical features, diagnosis and treatment of this infection are reviewed. Recent data exploring antigen-based serodiagnostics, the role of newer antifungals such as voriconazole, and the possibility of discontinuation of secondary prophylaxis after immune restoration from highly active antiretrovirals are discussed. SUMMARY: Large series from endemic areas and case reports from nonendemic regions have been published and provide insights into clinical features and presentation. Novel diagnostics are evolving, with galactomannan and other assays looking promising. Present therapy is largely based on noncontrolled studies, and further research into optimal therapy and the potential to discontinue secondary itraconazole prophylaxis is required.