The article describes the development of a new palette of genetically encoded Ca²⁺ indicators, including blue, improved green, red, and ratiometric indicators. These indicators were engineered to modulate their fluorescence in response to changes in calcium ion concentration, expanding the range of colors available for intracellular Ca²⁺ imaging. The researchers used a colony-based screen to evolve these indicators, leading to the creation of G-GECO1, G-GECO1.1, and G-GECO1.2, which exhibit significant improvements in Ca²⁺ sensitivity and signal-to-noise ratio compared to the previously available GCaMP3. Additionally, they developed B-GECO1 and R-GECO1, which provide blue and red fluorescence, respectively, and GEM-GECO1, a ratiometric indicator with an 11,000% ratio change. These indicators were tested in HeLa cells, neurons, and *Caenorhabditis elegans*, demonstrating their utility in multicolor Ca²⁺ imaging and simultaneous imaging of Ca²⁺ and adenosine 5′-triphosphate (ATP). The expanded palette of indicators opens new avenues for studying intracellular signaling and neuronal activity.The article describes the development of a new palette of genetically encoded Ca²⁺ indicators, including blue, improved green, red, and ratiometric indicators. These indicators were engineered to modulate their fluorescence in response to changes in calcium ion concentration, expanding the range of colors available for intracellular Ca²⁺ imaging. The researchers used a colony-based screen to evolve these indicators, leading to the creation of G-GECO1, G-GECO1.1, and G-GECO1.2, which exhibit significant improvements in Ca²⁺ sensitivity and signal-to-noise ratio compared to the previously available GCaMP3. Additionally, they developed B-GECO1 and R-GECO1, which provide blue and red fluorescence, respectively, and GEM-GECO1, a ratiometric indicator with an 11,000% ratio change. These indicators were tested in HeLa cells, neurons, and *Caenorhabditis elegans*, demonstrating their utility in multicolor Ca²⁺ imaging and simultaneous imaging of Ca²⁺ and adenosine 5′-triphosphate (ATP). The expanded palette of indicators opens new avenues for studying intracellular signaling and neuronal activity.