For nearly 50 years CCD (charge-coupled device) sensors and CMOS (complementary metal-oxide semiconductor) sensors have competed on cost and performance in a wide range of digital imaging applications. Peltier coolers (thermoelectric modules) have cooled both technologies when the requirement demanded high-resolution images. Design engineers opted to use CCD’s for astrophotography, super-resolution microscopy, x-ray crystallography, and spectrophotometric assays. On the other hand, CMOS sensors made inexpensive digital photography a reality. Recently, CMOS sensors have made advances into areas traditionally held by CCD sensors, as well as emerging applications such as imaging for autonomous systems, machine vision & learning, and object detection & recognition. In these existing and new uses, active spot cooling using Peltier coolers (thermoelectric modules) have enabled these new and innovative CMOS sensors to outperform CCDs at a lower cost point.