Plants, rooted in one place, are constantly subjected to diverse biotic and abiotic stresses that limit their growth and development, resulting in significant crop losses. In response to stresses, plants deploy several integrated signaling networks to rapidly reprogram gene expression thereby altering cellular processes to adapt and survive under unfavorable conditions. Among the key signaling mechanisms that plants use, calcium- and calcium/calmodulin- mediated signal transduction pathways have emerged as one of the ubiquitous players. The calcium-signaling networks include many calcium and calcium/calmodulin-binding transcription factors. In this review, we focus on the functions of a family of highly conserved calcium/calmodulin-binding Transcription Factors (TFs) called calmodulin-binding transcription activators (CAMTAs) in plants. This family of transcription factors was first identified in plants as calmodulin-binding proteins and discovered later in animals. Genetic studies in the model plant Arabidopsis and crop plants such as rice uncovered crucial roles for CAMTAs in modulating plant responses to both biotic and abiotic stresses. Depending on the type of stress, CAMTAs function as either positive or negative regulators for plant growth and stress responses. Arabidopsis CAMTA3 is the most studied member of CAMTA proteins. It modulates the expression of many key genes involved in different hormone signaling pathways and plays a central role in biotic (bacterial, fungal, and viral pathogens) as well as abiotic (cold, drought, salt, and wounding/mechanical) stress responses. Studies with many point, truncated, loss-of-function, and suppressor mutants of CAMTA3 revealed a complex regulation of its function. Here we summarize the advances in the study of the CAMTA family with a focus on CAMTA3. Further, we identify critical gaps in furthering our understanding of the molecular mechanisms by which these TFs function and discuss potential opportunities to engineer them for biotechnological applications to develop stress-resilient crops.