Despite improved overall survival rates after potentially curative liver resection (~50-58% at 5 years), almost half of patients experience disease recurrence highlighting the need for a precise definition of outcomes to stratify patients for clinical trials and to guide treatment decisions. In the past, several factors, such as an advanced primary T stage, the primary N+ status, a large tumor size, multiple tumors, a disease-free interval of <12 months, an elevated carcinoembryonic antigen level, the presence of an extrahepatic disease, and the margin width (<1 cm) and status (positive), have been recognized to predict poor outcomes, but most of them lack the sensitivity for accurate individual prognostication. Thus, in recent years, new factors, such as response to chemotherapy, either clinical or pathological, that more closely reflect tumor biology have been established and adopted in the clinical practice. Similarly, biomarkers of poor prognosis, especially mutations in KRAS and BRAF and the expression of thymidylate synthase, have been studied, yielding promising results. However, robust evidence of their prognostic utility awaits prospective validation.