Understanding of a disease and its treatment relies heavily on visualizing cells, tissues, and organs, making micro- and macro-imaging modalities integral to the biomedical community. Macro imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are still the mainstay of whole-body imaging because of their non-invasive nature and live image feed. However, they fail to deliver cellular details required to understand a disease or effectiveness of a treatment. On the opposite end of the spectrum, benchtop microscopes and histology can deliver excellent cellular resolution, allowing one to visualize cellular and intracellular interactions to better understand a disease, its progression and/or the outcome of therapies. However, to look at the cells, the tissue needs to be resected, fixed, processed, and stained before imaging. This whole process of visual confirmation may take hours to days. Deciding on these two imaging modalities always involves a compromise, either in time, resolution, or invasiveness. Confocal laser endomicroscopy (CLE) fills a unique niche between these macro- and micro-imaging modalities as it facilitates non-invasive to minimally invasive in vivo image acquisition in real time. In this two-part series we first examine the equipment available for CLE, and in the second part we will explore several applications of the technology.