BLAST remains one of the most widely used tools in computational biology. The rate at which new sequence data is available continues to grow exponentially, driving the emergence of new fields of biological research. At the same time, multicore systems and conventional clusters are more accessible. ScalaBLAST has been designed to run on conventional multiprocessor systems with an eye to extreme parallelism, enabling parallel BLAST calculations using >16 000 processing cores with a portable, robust, fault-resilient design that introduces little to no overhead with respect to serial BLAST.