Chemotherapy is, on its own or in combination with other treatments, a very effective anticancer therapy. Introduced in the middle of the last century, chemotherapy today still faces the problem of determining which specific agent or agents are able to yield the desired clinical therapeutical effect for a particular tumor and patient. Numerous tests in vitro have been developed to detect chemosensitivity and chemoresistance and also for screening new drugs. Three groups of tests can be defined: 1, cell viability tests; 2, measurements of cell metabolism; and 3, clonogenic assays. Test time, tissue preparation, complexity of test performance, and correlation with the clinical progress of the disease are criteria used to judge how successful the tests are. The introduction of Si-sensor chips, which are able to detect metabolic changes in living cells, has opened up new possibilities in this field. Basically two sensor principles or types can be considered: (a) the light-addressed potentiometric sensor (LAPS) and (b) the multisensor array (MSA). Whereas LAPS measures one, MSA registers online many parameters (for instance, impedance, pH, O2, temperature). The aim of this chapter is to review this technology and to present recent applications using cells, tissue slices, and biopsies.