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Oxygen photoreduction in chloroplasts in the Mehler reaction is amongst the well-known, but still confusing topics in photosynthesis. The history of this problem dates back to the 1951 when Alan Mehler had discovered hydrogen peroxide (H2O2) production in thylakoids under illumination. The most controversial topics were the intensity and the role of the Mehler reaction under environmental stresses. In the beginning of the 21st century the statement about the low rate of O2 uptake in chloroplasts was declared and the significance of this reaction was diminished. However, modern experimental technologies have rapidly extended our knowledge on H2O2-dependent signal transduction in plant. Current data on wide range of plant responses triggered by H2O2 accumulated in chloroplasts allow proposing that the Mehler reaction plays an important role in stress sensing and redox signaling. Although appreciable gaps are remaining in this area. Mechanisms that regulate H2O2 generation and accumulation in chloroplast are amongst the unresolved questions. It is supposed that potential ability to form reactive oxygen species in multiple sites of photosynthetic electron transport chain that was established from in vitro studies may be one of the crucial points for the in vivo regulation of the chloroplast signal transduction. The key intermediates and mechanisms of the signal transduction initiated from the Mehler reaction are not clear yet. To assemble the entire cell redox signaling network, we should use all benefits of classical biochemical and biophysical approaches with cooperation of the modern molecular biological and bioinformatics technologies.