In recent years, there has been growing interest in optically-encoded or tagged functionalized microbeads as a solid support platform to capture proteins or nucleotides which may serve as biomarkers of various diseases. Multiplexing technologies (suspension array or planar array) based on optically encoded microspheres have made possible the observation of relatively minor changes in biomarkers related to specific diseases. The ability to identify these changes at an early stage may allow the diagnosis of serious diseases (e.g. cancer) at a time-point when curative treatment may still be possible. As the overall accuracy of current diagnostic methods for some diseases is often disappointing, multiplexed assays based on optically encoded microbeads could play an important role to detect biomarkers of diseases in a non-invasive and accurate manner. However, detection systems based on functionalized encoded microbeads are still an emerging technology, and more research needs to be done in the future. This review paper is a preliminary attempt to summarize the state-of-the-art concerning diagnostic microbeads; including microsphere composition, synthesis, encoding technology, detection systems, and applications.