Cadmium is one of the highly toxic transition metals for human beings and is known as a human carcinogen. Once humans are exposed to Cd(2+) on a chronic basis, Cd(2+) primarily accumulates in the liver and kidney where it forms complexes with small peptides and proteins via sulfhydryl groups. Complexed Cd(2+) or the ionic Cd(2+) is then taken up by target cells and tissues and exerts the toxicity. However, the question of how non-essential Cd(2+) crosses the cell membranes remains unanswered. Furthermore, the molecular mechanism of Cd(2+)-induced physiological signaling disruption in cells is still not fully elucidated. Investigations of Cd(2+) uptake kinetics, distributions, and concentrations in cells require chemical tools for its detection. Because of the easy use and high spatiotemporal resolution, optical imaging using fluorescence microscopy is a well-suited method for monitoring Cd(2+) in biological samples. This chapter summarizes design principles of small molecule fluorescent sensors for Cd(2+) detection in aqueous solution and their photophysical and metal-binding properties. Also the applications of probes for fluorescence imaging of Cd(2+) in a variety of cell types are demonstrated.