Classical molecular genetic strategies have succeeded in identifying mutations responsible for numerous rare diseases with Mendelian patterns of inheritance, but have been largely unsuccessful in unravelling the (genetic basis of complex medical conditions like cardiovascular disease' diabetes and mental illness. These common disorders are shaped by multiple genes that exert weak allelic effects in the setting of confounding environmental variables. Association study designs provide statistical povwer to reveal the modest contributions of weak alleles, and evidence is mounting that common genetic polymorphisms play a role in complex diseases. Cataloguing genetic variation in human populations is a prerequisite for further validation of the 'common variants-common disease' hypothesis, and polymorphism discovery has begun in earnest in the academic and private sector. We will review several strategies for high-throughput polymorphism discovery and discuss the implications of early results from polymorphism screens for future genetic studies.