Since the first biosensor was introduced in 1962 by Clark and Lyons, there has been increasing demand for such analytical devices in diagnostic applications. Research initially focussed mainly on detector principles and recognition elements, whereas the packaging of the biosensors and the microfluidic integration has been discussed only more recently. However, to obtain a user-friendly and well-performing analytical device, those components have to be considered all together. This review outlines the requirements and the solutions suggested for the integration of suitable biosensors in packaging and the integration of those encapsulated biosensors into a microfluidic surrounding resulting in a complete and efficient analytical device for diagnostic applications. The components required for a complete biosensor instrument are described and the latest developments which meet the requirements for diagnostic applications, such as single-use components and arrays for multiparameter detection, are discussed. The current state and the future of biosensors in the field of clinical diagnostics are outlined, particularly on the basis of label-free assay formats and the detection of prominent biomarkers for cancer and autoimmune disorders.