Over the past two decades, despite the tremendous research effort performed on chemical sensors and machine olfaction to develop micro-sensory systems that will accomplish the growing existent needs in personal health (implantable sensors), environment monitoring (widely distributed sensor networks), and security/threat detection (chemo/bio warfare agents), simple, low-cost molecular sensing platforms capable of long-term autonomous operation remain beyond the current state-of-the-art of chemical sensing. A fundamental issue within this context is that most of the chemical sensors depend on interactions between the targeted species and the surfaces functionalized with receptors that bind the target species selectively, and that these binding events are coupled with transduction processes that begin to change when they are exposed to the messy world of real samples. With the advent of fundamental breakthroughs at the intersection of materials science, micro/nano-technology, and signal processing, hybrid chemo-sensory systems have incorporated tunable, optimizable operating parameters, through which changes in the response characteristics can be modeled and compensated as the environmental conditions or application needs change. The objective of this article, in this context, is to bring together the key advances at the device, data processing, and system levels that enable chemo-sensory systems to adapt in response to their environments. Accordingly, in this review we will feature the research effort made by selected experts on chemical sensing and information theory, whose work has been devoted to develop strategies that provide tunability and adaptability to single sensor devices or sensory array systems. Particularly, we consider sensor-array selection, modulation of