Aptamers- short nucleic acid or peptide ligands- attracted considerable attention across various disciplines as target specific therapeutic, delivery vehicle and diagnostic tools. The applicability of aptamers - often termed as 'chemical antibodies' - continues to grow and possess certain edge over the antibody counterpart. In this special issue, we have invited seven contributors to highlight the chemical biology, therapeutic, biosensor and imaging applications of aptamers. Furthermore, the issue end with an outlook of aptamer technology after 25 years of history.