Electronics has been working beyond the microscope well before the modern era of nanotechnology. Ultra-fast counters, single-particle detectors have been instruments of investigations since decades now. Additionally, electronic systems played a pivotal role in the progress of biosciences, for example, by allowing single ion channel recording in the early days of electrophysiology or by providing the necessary signal amplification during the discovery of atomic force microscopes. The role of integrated silicon regarding bioelectronic systems has been recently even more effective due to the device area reduction, allowing smart arrangement of interfaces onto arrays. Interestingly, even if the technology scaling is not favorable with respect to the signal to noise ratio, there is a remarkable trend over the last decade about interface performances confirmed by several figures of merit. The paper will show how circuit techniques and reduction of stray capacitance play a crucial role on the improvements of performances. Recent trends of the design of microelectronic interfaces to cope with biological entities using CMOS substrates will be reviewed by discussing the design trade-offs and the trends with respect to the scaling in both sensing and actuation.