Cryptic genetic variation (CGV) is invisible under normal conditions, but it can fuel evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles that are in need of constant suppression. CGV emerges from both neutral and selective processes, and it may inform about how human populations respond to change. CGV facilitates adaptation in experimental settings, but does it have an important role in the real world? Here, we review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution.