As a distinct discipline, Metabolic Engineering (ME) was not conceived until the early 1980s, and became more extensively understood starting in about 1992. After the formative years of extensive computational and experimental network and pathway analysis, the era of genome sequences and more broadly experimental and computational genomics had arguably the biggest impact in accelerating progress and creating new platforms and paradigms for ME. We are now at crossroads as to of the evolution and impact of the field: pathway analysis of all kinds (in vivo, in vitro and in silico), synthetic biology of the deterministic, small-scale kind, chemical-biology or library-driven forced diversity, shuffling of genes and genomes, and in vivo forced evolution, are now at the center of the much broader field, which started as a rather lonely activity among some pioneers in chemical engineering, but has been now embraced by the whole community in life sciences, and beyond.