Highly effective, well-tolerated interferon-free direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with the opportunity for broad treatment scale-up among marginalised or "high-risk" populations, including people who inject drugs (PWID) and people with HIV/HCV coinfection.Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID. However, the incidence of reinfection following interferon-based treatment for chronic HCV is low among PWID. Reinfection rates in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence reported in some cohorts. Mathematical modelling suggests that substantial reductions in HCV incidence and prevalence could be achieved with targeted DAA therapy among those at the highest risk of ongoing transmission. This review will summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV coinfection, discuss the individual- and population-level impact of DAA treatment scale-up and reinfection, and highlight ongoing and future research questions in expanding HCV care and treatment to those populations at high risk of ongoing HCV transmission.