Given the interest of CYP51 as a drug target and the severity of disease caused by T. brucei, we investigated the essentiality of T. brucei CYP51 and we evaluated the effect of posaconazole alone and in combination with eflornithine in vitro and in a murine model of African trypanosomiasis. The gene discussed is CYP51A1; the disease is human African trypanosomiasis.