Invasive fungal infections (candidiasis, aspergillosis and cryptococcosis) are major complications in immunocompromised patients and account for high morbidity and mortality. Guidelines on first-line therapy of invasive fungal infections are based on randomised clinical trials or experts' guidelines and include essentially single antifungal therapies, except for cryptococcosis. However, the severe prognosis of these infections raises the interest of antifungal associations, in first line or second-line therapy, and many experimental data have been published on this issue. In humans, amphotericin B plus flucytosine combination therapy in cryptococcal meningitis has been largely validated, especially in HIV-infected patients. Also, a few studies demonstrated that the combination of fluconazole plus amphotericin B in candidiasis is not antagonistic and that caspofungin plus polyene or caspofungin plus azole combinations may be beneficial in invasive aspergillosis. Randomised studies are necessary to confirm these data. A study assessing anidulafungin plus voriconazole association in aspergillosis is oncoming.