Hepatitis C virus infection is associated with increased morbidity and mortality. It remains a major challenge for management and treatment, especially in patients with renal transplant. The new direct-acting antiviral agents gave big hopes to both clinicians and patients that they can overcome this challenge without major side effects. Studies recently have supported this claim; however, they are still few, limited, and may give false hopes. In the following case report, we present a case, supported by histological evidence about a possible acute rejection of kidney transplant after treatment with these new medications. This case is limited by the absence of donor-specific antibodies. This report is aimed to increase awareness about the urgent need for further studies.