The development of synthetic biology opens up new possibilities for the construction of efficient H2 evolving cyanobacterial strains. An obstacle in biological H2-production is the oxygen sensitivity of the H2 evolving enzymes. Some attempts have already been made to introduce less oxygen sensitive hydrogenases into cyanobacteria. An elegant strategy for the creation of more efficient H2 producers would therefore be the expression of more efficient noncyanobacterial hydrogenases, for example FeFe-hydrogenases with higher turnover rates, in the anaerobic environment of the heterocysts of a filamentous cyanobacterium. Since protons are abundant within the cell, the main limitation for H2-production is the rate of supply of reducing equivalents. The primary electron donors for the H2 producing enzymes are ferredoxin (nitrogenase and FeFe-hydrogenases) and NAD(P)H (NiFe-hydrogenases). However, these reductants are also used by competing pathways like respiration. Therefore, it will be important to direct the electron flow toward the H2 producing enzymes and away from competing pathways. As the cyanobacterial bidirectional hydrogenase evolves H2 at relatively high levels of NAD(P)H, the construction of mutants with blocked electron transfer in selected key pathways may be a promising route to increased H2-production. Answers to questions as to how much of the maturation system needs to be introduced and translated into functional units, and what kind of regulation is needed, will be crucial for success.