Background: Hepatocellular carcinoma (HCC) is the most deadly complication of all major chronic liver diseases. Since early detection is the most significant determinant of overall survival, intense screening is of major importance. Methods: This overview is based on a systematic review of the available literature on HCC screening and surveillance in the PubMed database. Results: Over the last decades, major etiological risk factors were identified and the population at highest risk for the development of HCC was clearly defined. Screening in these patients has been repeatedly demonstrated to detect early tumor stages and to be cost-effective. Therefore, screening is recommended by all current guidelines and usually comprises a bi-annual ultrasound examination in Western countries. In some Asian countries biomarkers are also used; however, their efficiency for Western HCCs remains to be determined. The detection of lesions >1 cm during routine screening requires subsequent confirmation of HCC. The diagnosis can be accurately established by modern imaging techniques, i.e. computed tomography or magnetic resonance imaging, in the majority of patients. In ambiguous cases and if radiological criteria are not met by two imaging techniques, biopsies remain the gold standard for diagnosis. Furthermore, histology is of key importance for the development of new diagnostic and predictive biomarkers. Conclusion: Screening and detection algorithms for patients at risk for HCC are effective and should be rigorously implemented in clinical routine.