Abdominal ultrasound has been the cornerstone of hepatocellular carcinoma (HCC) surveillance for years given several advantages including being readily available, non-invasive, relatively cheap, and acceptable test performance. However, there has been increasing recognition of ultrasound’s limitations including operator dependency and suboptimal sensitivity for early-stage HCC detection when used alone, particularly in contemporary cohorts with higher prevalence of obesity and non-viral etiologies of liver disease. Alpha fetoprotein (AFP) appears complementary to ultrasound, significantly increasing sensitivity for early-stage HCC detection with only a small, clinically insignificant decrease in specificity. Several emerging biomarker panels have promising performance for HCC surveillance, either alone or in combination with ultrasound; however, these require prospective validation prior to adoption in clinical practice.