Clinical diagnosis of chronic hepatitis C infections is a difficult task. This is due to the insidious nature of the infection and the subclinical and symptomless presentation in the majority of cases. The laboratory plays a principal role not only in the specific diagnosis of the infection but also in assessing the severity and evolution of the liver disease, selection of patients for therapeutic intervention, monitoring treatment and determining the outcome of treatment. To attain these goals, improvements in sensitivity and specificity of various techniques, including molecular diagnostic assays, have been introduced. Most importantly, patients may be excluded if they have conditions that are contra-indicated for treatment as determined by laboratory parameters. In cases of adverse events the drugs may be reduced or withdrawn based on clinical and laboratory results. The improvement over the last decade of laboratory assays has paralleled the success in the sustained response rates reported for hepatitis C virus treatment. A good laboratory provides the tools for diagnosis and treatment essential for good management. This is a multidisciplinary approach involving all branches of pathology.