The only curative treatment option for hepatocellular carcinoma patients is either a surgical resection or liver transplantation. Due to limited supply of donor organs and the stringent selection criteria for liver transplantation, resection is the mainstay of therapy, particularly for patients with preserved liver function and small tumors with no portal hypertension. However, tumor recurrences and subsequent death is common after resection, which has prompted a search for an effective adjuvant therapy to improve patient outcomes. Studies have looked at various adjuvant treatment modalities, including systemic chemotherapy, intra-arterial approaches with or without chemotherapy, and the use of cytokines, but there is still no established role for adjuvant therapy after a curative liver resection. Unfortunately, many of these trials lack adequate sample sizes, and are heterogeneous in the patient populations and study end points, thereby limiting robust conclusions. Based on current available data, the role of adjuvant therapy after liver resection needs to be further investigated. The use of molecular targeted therapy focusing on the vascular endothelial growth factor pathway appears to be a promising step. Clinical trials assessing adjuvant therapies after a curative liver resection are urgently needed. These should ideally be prospective, randomized trials with properly selected patients and appropriate end points.