The management of patients with chronic liver disease (CLD) requires an accurate definition of the staging and grading, as the latter is related to the progression of liver fibrosis. Albeit liver biopsy (LB) is an invasive procedure with possible complications, it is currently the "gold standard" for the assessment of hepatic fibrosis. Over the past decade, several noninvasive approaches have been proposed as surrogates in the evaluation of liver fibrosis. These include serum direct and indirect markers of fibrosis linked, respectively, to fibrogenesis and hepatic function, and instrumental techniques, which measure liver stiffness, a parameter directly correlated with liver fibrosis. Although accuracy of noninvasive methods was initially investigated in chronic hepatitis C, there are now increasing data referred to their application in other CLDs. While in specific settings, there is still need for LB, noninvasive methods have an increasing and crucial role in clinical practice to monitor fibrosis progression in patients with CLD. The aim of this review is to present the current status of knowledge in this new exciting field and to highlight the key messages useful for clinicians.