Since traditional chemical processes are non-renewable and environmentally unfriendly, biosynthesis is emerging as an attractive alternative for the production of advanced biofuels, chemicals, pharmaceuticals and polymers. Cost-competitive biomanufacturing requires the design of metabolic pathways that can achieve high production yields and rates. Recent advances in natural amino acid production have motivated the use of 2-ketoacid intermediates for the production of important chemicals. These 2-ketoacids undergo a wide range of efficient biochemical reactions leading to an array of industrially useful products. In this review, recently developed novel pathways based on 2-ketoacids will be described along with representative examples.