Chronic hepatitis C virus (HCV) infection is a systematic disease that affects several aspects of patients’ well-being, including physical, mental, social, and sexual quality of life. In recent years, there has been a growing body of literature focusing on HCV patients’ sexual health, providing evidence of clinically significant and enduring disturbances that disrupt everyday living, but commonly evade clinicians’ attention. Relevant studies are characterized by considerable methodological heterogeneity and their findings should be interpreted using a systematic and integrative approach. In this context, we performed a systematic literature review on the topic of HCV patients’ sexual functioning aiming at identifying high-quality investigations reporting scientifically sound and clinically useful data. We performed a thorough search of PudMed, ScienceDirect, and GoogleScholar according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Twenty-five articles were included to the review, reporting data from over 5300 chronic HCV patients. Sexual dysfunction, predominantly in the domains of sexual desire, drive, and satisfaction, is commonly reported by HCV patients at rates ranging between 19 and 88%. The current review yielded three distinct patterns of sexual impairment, namely, precirrhotic sexual impairment, cirrhosis-induced sexual decline, and interferon-associated sexual difficulties. Our search yielded significant findings on the prevalence, the characteristics, and the determinants of HCV-associated sexual dysfunction. In addition, we detected several areas of scientific controversy and inadequate information, thus highlighting novel directions for future research.