Even if the first published article on a porous silicon (PSi)-based biosensor dates back to more than twenty years ago, this technology still attracts great attention from many research groups around the world. In this brief review, the pros and cons of porous silicon-based optical biosensors will be highlighted on the basis of some recent results and published papers on this subject. The aim of the paper is to give a straightforward introduction to PhD students and young researchers on this subject, which is particularly full of educative content, since it is highly multidisciplinary. Fabrication of PSi-based optical biosensors requires competencies related to many different scientific topics ranging from material science, physics and optics to healthcare and environmental monitoring through surface chemistry and more.