Both response to treatment as well as spontaneous outcome of hepatitis C virus infection is critically affected by host genetic factors. However, most of the identified association genes could not be confirmed in subsequent studies and almost none of the identified risk factors had a noticeable impact on clinical decisions. In contrast, recent land-mark studies identified variations in close proximity to the interleukin 28B gene locus to be independently associated to treatment response and spontaneous viral clearance in hepatitis C genotype 1 infection. These findings and their potential role in future treatment decision-makings will be discussed here.