The benzylisoquinoline alkaloids (BIAs) represent a large subset of plant secondary metabolites derived from tyrosine, which exhibit a range of pharmacological activities. A microbial strategy for alkaloid biosynthesis will present several advantages over natural plant-based systems including increased yields, cheaper production, a system for conducting rapid genomic screens, and accumulation of intermediates not observed in the native hosts. Progress on reconstructing a heterologous early BIA pathway in yeast will be discussed. Synthetic pathways comprised of enzymes cloned from a variety of organisms have been constructed for the de novo production of (S)-coclaurine. In addition, downstream recombinant pathways for the production of the major branch point molecule (S)-reticuline have been characterized by feeding the commercially available substrate norlaudanosoline. The integration of the early and downstream branches of these synthetic networks will be discussed. Finally, novel molecular sensors are being developed for real-time, noninvasive detection and regulation of key metabolite levels.