Within the spectrum of diagnostic procedures in hepatology, the procurement of a liver specimen plays an important role. Although diagnostic tests that employ seroimmunological, biochemical, molecular biologic, functional, as well as imaging techniques are capable of establishing the etiology of a chronic or acute liver disease, in most instances the gold standard for the assessment of stage as a common end point of progressive liver diseases is the histological evaluation of a liver sample. Since the first documented biopsy by Paul Ehrlich in 1883 by aspiration, the method has been diversified to encompass not only different needle types for cutting and aspiration but also different routes proceeding transvenously or transcutaneously, and in the combination with imaging modalities such as ultrasound, computed tomography, and laparoscopy. Standard liver biopsies can be rapidly performed and have an accepted mortality rate between 0.1% and 0.01%. The decision between different techniques is based upon the risk profile of the patient who very often has advanced liver failure with coagulopathy and ascites on the one hand and the underlying disease on the other hand. Although standard liver biopsy in hepatitis C infection or suspected rejection in a transplant patient is often sufficient, a laparoscopically guided biopsy can be of value in diseases such as primary sclerosing cholangitis or suspected metastatic disease, which are characterized by a zonal affection of the liver and possibly the peritoneum. Coagulopathy may lead to transjugular or plugged biopsies, and the workup of undetermined hepatic masses may favor ultrasound-guided aspiration cytology. Among the most feared complications of liver biopsies are hemorrhage, seeding of cancer cells, infections, and injury to the viscera. In view of these complications, a careful assessment of the clinical question, the appropriate invasive approach, and an expected management consequence are necessary. This requires a detailed consideration of the differences of biopsy techniques currently available to the clinical hepatologist.