Biocompatibility has undergone a change of emphasis in the past few years and is now generally accepted as involving two principal areas: the principle of b iosafety , which involves the exclusion of severe deleterious effects of the biomaterial on the organism. This encompasses both cytotoxicity as well as the field of mutagenesis and carcinogenesis. The second area is concerned with b iofunctionality , an aspect which includes b ioacceptance and deals with the a bility to perform with an appropriate host response in a specific application . Highly sophisticated cell culture techniques, in vitro systems and methods, have paved the way for the development of a variety of tests which are suitable for testing new materials as well as materials that are already employed in medical devices.In the context of biosafety, cytotoxicity testing is central to the International Standard (ISO 10993-5), which attempts to present guidelines for the choice of suitable tests and define important principles of these tests. In the ISO standard categories of evaluation are presented for assessment of cell damage by morphological means, measurement of cell damage, cell growth and specific molecules of cellular metabolism. The assessment of cell structural changes must be regarded as an appropriate method. However, we recommend, if possible, an evaluation of cytotoxic effects by quantitative additional methods. Examples of these are MTT-test, measurement of DNA synthesis and membrane integrity tests.Testing biofunctionality in vitro aims at establishing reproducible and quantitative assays which center on cells involved and biological parameters relevant to the medical device application. Cytotoxicity testing in vitro usually involves permanent cell lines, such as HeLa cells (derived from a human cervical carcinoma) or L-929 cells (a mouse fibroblast cell line). However, more than the tests mentioned above can equally well be carried out on primary isolated human cells. Thus, endothelial cells (EC) would be the logical choice for biofunctionality testing of vascular protheses, platelets, monocytes and granulocytes for all blood-contacting devices as described by the ISO standards for hemocompatibility testing (ISO 10993-4). Fibroblasts, chondrocytes and osteoblasts should be used for studying cell interaction with orthopaedic or dental implants. Further parameters include cell adhesion, cell spreading, proliferation, biosynthetic function, mediator release as well as the evaluation of the cell-biomaterial-interface. We regard this approach as the essential way to progress in the biomaterial application field beyond the philosophy of trial and error. The choice of suitable methods will have to guarantee the specificity, reproducibility and reliability of biomaterial testing in vitro.