Paracoccidioidomycosis is the most prevalent systemic endemic mycosis in South America with most reported cases in Brazil. It is a major cause of disability and death among young adult rural workers during their most productive years of life. Sequels are frequent and the evolution of the disease and mortality burden are strongly influenced by the socio-economic status of the patients. Although long periods of antifungal therapy (sulfamethoxazole/trimethoprim, itraconazole and amphotericin B) are used in clinical practice, relapses remain a significant unresolved problem. Early diagnosis is hampered by structural factors, ranging from the high costs of reagents, the lack of trained personnel and limited access to the healthcare system by rural workers. A peptide vaccine aimed at immunotherapy of paracoccidioidomycosis, as an adjuvant to chemotherapy, is being studied. The protective effects obtained in mice intratracheally infected with Paracoccidioides brasiliensis, and the promiscuous binding of the peptide P10 to HLA-DR molecules, suggest that it could be used as a vaccine to reduce the duration of chemotherapy and the risk of relapse.