Psychiatric difficulties,including depression and alcohol use disorders,pose a challenge to treatment decisionmaking for chronic hepatitis C.This is especially made worse because interferon-alpha,as part of the standard of care,may exacerbate depressive symptoms and cause suicidal symptoms to appear.This requires a treatment setting that has the capacity to carry out psychiatric assessment and monitoring,and the capability to deliver patient education regarding these aspects of care.Psychiatric comorbidities create a challenging decisionmaking situation,especially since success rates for the most common hepatitis C genotype,genotype 1,hover around 40%.In recent years,new treatments have emerged.These significantly boost the likelihood of sustained viral response,including for genotype 1,and do not seem to have the side effects of interferonalpha or ribavirin.Relevant data are reviewed to assess the degree that these new treatments might reduce the portion not eligible for treatment due to psychiatric comorbidities,and might reduce the emergence of psychiatric symptoms during treatment.Several organizations have recently released evidence-based treatment recommendation guidelines.It is apparent that interferon-alpha continues to be a standard of care,with the new drugs added to this recognized regimen in order to shorten treatment and to boost efficacy.Clinical settings must continue to assess appropriateness for treatment,including current or recent psychiatric comorbidities,and must continue to closely monitor patients for the emergence of psychiatric side effects.The newly developed hepatitis C treatments may affect the metabolism of several categories of psychiatric drugs,and so drug-drug interactions must also be considered and monitored.With many promising drugs under development,an all-pill regimen,with no interferon-alpha and no ribavirin,may emerge in the near future.This will greatly change the challenge of treatment decision-making,and should expand the portion of patients able to successfully complete