Understanding the interactions between planktonic prokaryotes and their controlling factors remains a challenge to fully comprehend microbial food webs in tropical and subtropical regions. The Red Sea is one such region, which can be considered extreme due to its elevated salinity and temperature values. The standing stock and productivity of prokaryotes are simultaneously controlled by bottom-up (i.e., resources availability) and top-down (i.e., protistan grazing and viral lysis) factors, with temperature also playing a paramount role. This dissertation aims at assessing the variability of planktonic prokaryotes, with a focus on heterotrophic prokaryotes, and their controls over various spatio-temporal scales in the Red Sea. We conducted two years of monthly samplings in inshore and offshore surface waters of the central Red Sea differing in their trophic status, and performed 4 microcosm experiments at the former site covering the seasonal cycle to determine the joint impact of nutrients and temperature on the abundance of bacterioplankton, heterotrophic nanoflagellates (HNFs) and viruses. We also conducted 11 vertical profiles (from 5 to 700-1000 m) along a latitudinal gradient from 16 ºN to 27 ºN. Sampling was also carried out in three brine pools (Suakin, Port Sudan and Afifi). Using flow cytometry, we distinguished 5 groups of heterotrophic prokaryotes based on their nucleic acid content, membrane state and respiration activity, 3 groups of autotrophic bacteria (Prochlorococcus and two Synechococcus groups), HNFs and 3 groups of viruses of differing nucleic acid content. Our findings indicate a persistent seasonal switch between HNFs and viruses in controlling the abundances of heterotrophic prokaryotes in surface inshore waters with offshore waters being more loosely controlled by top-down factors. Bacterioplankton and their top-down controls showed a greater response to inorganic and mixed nutrients additions than to temperature, suggesting that the impact of future warming in the Red Sea will be minor. Together, our results also support that strong top-down control is largely responsible for the low stocks of heterotrophic prokaryotes in the Red Sea compared with other tropical regions, with viruses being a more important source of mortality in brine pools. Overall, this dissertation provides detailed insights into the role of bottom-up and top-down controls in regulating prokaryotes abundances in the relatively less known tropical and subtropical waters.