Recent advances in therapy for patients with chronic hepatitis B (CHB) infection offer the potential for a more successful treatment outcome, but also raise a number of questions in clinical practice regarding diagnosis and staging of CHB to ensure such potential is realized. In patients without cirrhosis, some forms of antiviral therapy can switch patients from an active disease phase into an inactive hepatitis B surface antigen (HBsAg) carrier state, and eventually lead to HBsAg clearance and HBsAg antibody seroconversion, the closest to a cure in CHB; thus, one of the most important diagnostic questions that clinicians face is the identification of patients with early forms of CHB within a large cohort of asymptomatic HBsAg-positive individuals, most of whom are inactive HBsAg carriers. Two major categories of diagnostic markers are currently available: virus-specific markers and liver disease markers. Most markers involve the use of non-invasive serological testing, but invasive diagnostic procedures, such as liver biopsy, are also an option. In this article, we review current opinions on the appropriate use of diagnostic procedures, answering some important questions for the clinician, such as why, how, when and in whom they might best be used.