Cyanobacteria are among the oldest living organisms on this planet, existing since more than 3 billion years. They are ideal organisms for investigating biological processes such as photosynthesis, respiration, circadian rhythm, photoregulation of gene expression, developmental gene rearrangements, and specialized cell differentiation. They are nearly ubiquitous in distribution, have colonized a wide range of ecosystems including soil, air, dry rock, and aquatic systems, and even occupy extreme niches that are inaccessible to other organisms. Such wide ecological distribution reflects their capacity to acclimate to extreme environments. They show great adaptive abilities and have survived various adverse physiological growth conditions like desiccation, high temperatures, extreme pH, cold, osmosis, salt, light, nitrogen, and high salinity. Their ancient origin and surviving through numerous stresses during evolution indicates their remarkable capabilities to survive and prevail under different environmental and man-made stresses. It has been hypothesized that similar and overlap stress response mechanisms help them to survive different stresses. It has been stated that responses against stresses like radiation has been accidental-exhibited because of similar response against desiccation stress, which has prevailed more during evolution. These overlaps and similarities in stress responses have been instrumental in making these organisms a large class of biological entities today. Present review discuss about stress tolerance in cyanobacteria against two extreme stresses - desiccation and gamma radiation. It also discuss the commonality and underlying molecular mechanisms in these two stress responses.