This volume contains the proceedings of the 21st Annual International S- posium on Algorithms and Computations (ISAAC 2010), held in Jeju, Korea during December 15-17, 2010. Past editions have been held in Tokyo, Taipei, Nagoya,HongKong,Beijing,Cairns,Osaka,Singapore,Taejon,Chennai,Taipei, Christchurch, Vancouver, Kyoto, Hong Kong, Hainan, Kolkata, Sendai, Gold Coast, and Hawaii over the years 1990-2009. ISAACis anannualinternationalsymposiumthatcoversthe verywide range of topics in algorithms and computation. The main purpose of the symposium is to provide a forum for researchers working in algorithms and the theory of computation where they can exchange ideas in this active research community. In response to the call for papers, ISAAC 2010 received 182 papers. Each submission was reviewed by at least three Program Committee members with the assistance of external referees. Since there were many high-quality papers, the Program Committee's task was extremely di?cult. Through an extensive discussion, the Program Committee accepted 77 of the submissions to be p- sented at the conference. Two special issues, one of Algorithmica and one of the International Journal of Computational Geometry and Applications,were prepared with selected papers from ISAAC 2010. The best paper award was given to "From Holant to #CSP and Back: c DichotomyforHolant Problems"byJin-YiCai,SangxiaHuangandPinyanLu, and the best student paper award to "Satis?ability with Index Dependency" by Hongyu Liang and Jing He. Two eminent invited speakers,David Eppstein from UniversityofCalifornia,Irvine,andMattFranklinfromUniversityofCalifornia, Davis, also contributed to this volume.