This book constitutes the refereed proceedings of the 21st International Conference on DNA Computing and Molecular Programming, DNA 21, held in Boston and Cambridge, MA, USA, in August 2015. The 13 full papers presented were carefully selected from 63 submissions. Presentations are sought in all areas that relate to biomolecular computing, including, but not restricted to: algorithms and models for computation on biomolecular systems; computational processes in vitro and in vivo; molecular switches, gates, devices, and circuits; molecular folding and self-assembly of nanostructures; analysis...