Microelectronics is fostering the realization of revolutionary and smart micro-analytical systems for biomedical applications, in particular for early, point-of-care diagnostics and treatment monitoring. Despite potentially huge markets and widespread research efforts, still only a few successful examples are consolidating in the market. In this paper we review the state of the art of CMOS-compatible circuits and microsystems for detection of bio-molecules. Advances and open issues in detection mechanisms (electrochemical, optical, magnetic and emerging ones), readout circuits and fabrication, packaging and interfacing approaches are discussed. Novel circuit solutions are addressing several challenges including: ultra-high sensitivity (i.e. low-noise), low power and low area occupation to integrate up to thousands of parallel sensing channels, preserving satisfactory performance.