Cell-substrate adhesion is a critical factor in the development of biomaterials for use in applications such as implantable devices and tissue engineering scaffolds. In addition, cell adhesion to the extracellular matrix is intertwined with a number of fundamental cell processes, and several diseases are characterized by cells with altered adhesion properties. While many approaches exist to characterize cell adhesion, only a fraction of the techniques provides quantitative measurements of the strength of adhesion by physically detaching cells through application of force or stress. In this review, the most commonly used techniques to measure the adhesion strength of cells adhered to substrates are summarized. These methods can be divided into three general categories: centrifugation, hydrodynamic shear and micromanipulation. For each method, the technique is described and its capabilities assessed. A comprehensive review of recent applications of the methods is given, and adhesion strength measurements performed using different techniques on fibroblasts, a commonly-studied cell, are compared. Finally, the strengths and drawbacks of the various techniques are discussed. (C) Koninklijke Brill NV, Leiden, 2010