Most protein design efforts to date have focused on reengineering existing proteins found in nature. By contrast, de novo protein design generates new structures from scratch, with sequences unrelated to naturally occurring proteins. Before 2011, the only successful de novo designed proteins were Top7 (2003), and an array of coiled coil peptides (helical bundles). In the past five years, the field of de novo protein design has exploded. The wealth of new structures, and advancements in methodology, should now now allow proteins to be precisely crafted and custom-made to solve specific modern-day problems.