Functional immunoassays measure a change in function of a molecular, cellular or multicellular system, when antibodies are used to block, stimulate or modulate specific biological triggers. This chapter is limited to functional immunoassays conducted on cultured cells in vitro. Since impedance-based monitoring of cultured, adherent cells is an established technique to monitor cell attachment, spreading, proliferation, migration or polarization, it has evolved to a powerful readout capable of following functional changes induced by specific antibodies interacting with molecular key components of this function. The most obvious advantages of impedance-based analysis are the label-free, non-invasive and time-resolved readout so that not only the endpoint of a gain or loss of function is assessable but also its kinetics. This survey summarizes the principles of impedance-based cell monitoring, best practice workflows and reported examples for functional immunoassays including such timely applications as antibody-dependent cytotoxicity or immune cell-mediated cell killing. When impedance-based cell monitoring is combined with in situ electroporation, intracellular antigens get also accessible for immunomodulation and intracellular manipulation. This combined intracellular antibody delivery and cell monitoring approach is highlighted at the end. Impedance-based cell monitoring by itself lacks molecular specificity. Combination with components of the immune system closes the gap.