The fixed dose combination of ledipasvir-sofosbuvir provides a very attractive and effective one pill once a day option for treatment of genotype 1 chronic hepatitis C infection. This regimen is the first FDA-approved interferon- and ribavirin-free regimen to treat hepatitis C. Three phase 3 trials (ION-1, ION-2, and ION-3) have demonstrated SVR rates consistently above 90%. For treatment-naive, non-cirrhotic patients who have a pretreatment HCV RNA level less than 6 million IU/ml, use of the shorter 8-week regimen is justified and will provide a major cost savings over the 12-week regimen (and it is less expensive than a 12-week regimen of sofosbuvir plus ribavirin). The 24-week regimen for treatment-experienced cirrhotic patients is prohibitively expensive. Insufficient data exist to recommend the use ledipasvir-sofosbuvir in genotypes other than genotype 1. Although ledipasvir-sofosbuvir is not specifically FDA-approved for HIV-infected patients, it will likely generate significant interest for use in this arena.