Biomarker discovery is essential to the advancement of our knowledge about diseases and to the development of new strategies for treatment and therapy. Among the newest technologies in this rapidly growing field is a process termed Cell SELEX by which a panel of aptamers can be generated to specifically target disease cells. Thus, Cell SELEX, together with the in vitro selection of aptamers, brings a promising approach to accelerate the progress of biomarker discovery. In this review, the Cell SELEX method and potential uses of selected aptamers are discussed. In addition, identification of potential biomarkers by using cell-binding aptamers is addressed. We believe that using the Cell SELEX strategy represents a significant improvement over current approaches to biomarker identification by the simplicity, efficiency and specificity of its application.