Marine macroalgae, commonly known as seaweeds, are assemblage of diverse groups of phototrophic marine plants and form the base of the marine trophic pyramid. Rocky intertidal zones are the most dynamic and comprises of highly stressful habitats for marine life including seaweeds. They often experience severe environmental stress as a result of periodic exposure to a wide range of ambient conditions including intense radiation, high temperature, desiccation and salinity with turning tides. The relative abundance, survivability and distribution of seaweeds in such environments are principally determined by their tolerance abilities to diverse environmental stresses. Any adverse effect on seaweeds as a result of fluctuating environmental conditions can directly or indirectly lead to perturbations at higher trophic levels and eventually affect the integrity and sustainability of aquatic ecosystems. The recent proteome, transcriptome, metabolome and other biochemical analysis of seaweeds under oxidative stress have suggested the involvement of mannitol, proline, abscisic acid, polyamines, polyunsaturated fatty acids, oxylipins and fatty acid desaturases among others defending the seaweeds from diverse environmental stress. Both salinity and desiccation stresses are comparable in the context of a reduction of cellular water potential but differ in physiological process of ions uptake and their ratio determines the acclimation potential of seaweeds. In this chapter, we describe various tolerance and adaptive strategies of seaweeds in response to salinity fluctuations and desiccation induced oxidative stress at both biochemical and molecular levels enabling them to endure successfully for extended periods of stresses. Further, the new opportunities that became available from whole genome sequences of the brown alga Ectocarpus siliculosus and the red alga Chondrus crispus, in gaining newer insights into the cellular mechanisms of stress tolerance at molecular level in seaweeds is also discussed.