Most of the research to date on cyanobacterial uptake hydrogenases has been performed on filamentous heterocystous strains. However, recent results on the hup gene cluster organization and its transcriptional regulation in non-heterocystous strains has contributed to the widening of knowledge in this field. In the present study, we outline the recent findings on uptake hydrogenases from non-heterocystous cyanobacteria, comparing it with the presently available data from heterocystous strains, and draw attention to potential areas for future research.