The ability to assess health status, disease onset and progression, and monitor treatment outcome through a non-invasive method is the main aim to be achieved in health care promotion and delivery and research. There are three prerequisites to reach this goal: specific biomarkers that indicates a healthy or diseased state; a non-invasive approach to detect and monitor the biomarkers; and the technologies to discriminate the biomarkers. The early disease diagnosis is crucial for patient survival and successful prognosis of the disease, so that sensitive and specific methods are required for that. Among the numerous mankind diseases, three of them are relevant because of their worldwide incidence, prevalence, morbidity and mortality, namely diabetes, cardiovascular disease and cancer. In recent years, the demand has grown in the field of medical diagnostics for simple and disposable devices that also demonstrate fast response times, are user-friendly, costefficient, and are suitable for mass production. Biosensor technologies offer the potential to fulfill these criteria through an interdisciplinary combination of approaches from nanotechnology, chemistry and medical science. The emphasis of this chapter is on the recent advances on the biosensors for diabetes, cardiovascular disease and cancer detection and monitoring. An overview at biorecognition elements and transduction technology will be presented as well as the biomarkers and biosensing systems currently used to detect the onset and monitor the progression of the selected diseases. The last part will discuss some challenges and future directions on this field.